US7091191B2 - Modified hyaluronic acid for use in musculoskeletal tissue repair - Google Patents

Modified hyaluronic acid for use in musculoskeletal tissue repair Download PDF

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US7091191B2
US7091191B2 US10/741,511 US74151103A US7091191B2 US 7091191 B2 US7091191 B2 US 7091191B2 US 74151103 A US74151103 A US 74151103A US 7091191 B2 US7091191 B2 US 7091191B2
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hyaluronic acid
chloride
complex
tissue
bzcl
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Walter R. Laredo
Alireza Rezania
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DePuy Orthopaedics Inc
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Ethicon Inc
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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
    • C08B37/0072—Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728—Hyaluronic acid

Definitions

  • the present invention is directed to hyaluronic acid complexes suitable for incorporation with tissue scaffolds that are suitable for use in muscoloskeletal tissue repair and/or regeneration.
  • HA hyaluronic acid
  • HA is a naturally-occurring linear polysaccharide comprised of D-glucuronic acid and N-acetyl-D-glucosamine.
  • the ionic polymer has a range of molecular weight of from 1,000–10,000,000 Daltons.
  • the use of purified HA has become common practice for treatments such as corneal transplantation, viscosupplementation of the knee, anti-adhesive barriers in spinal surgeries and wound healing applications.
  • HA has been explored as a scaffold to enhance the repair of tissue.
  • the poor physical properties of natural HA and its rapid resorption by the body has restricted its use to applications where a structurally sound scaffold is not required.
  • cross-linking agents include formaldehyde, glutaraldehyde, vinyl sulphone, biscarbodiimides, poly-functional epoxides, glycidyl ether, photocurable cinnamic acid derivatives and adipic dihydrazide.
  • cross-linking agents include formaldehyde, glutaraldehyde, vinyl sulphone, biscarbodiimides, poly-functional epoxides, glycidyl ether, photocurable cinnamic acid derivatives and adipic dihydrazide.
  • HA derivatives have been obtained by targeting specific functional groups of HA, such as carboxyl, hydroxyl and N-acetyl groups through chemical reactions, such as esterification, acylation, amidation, and sulphation.
  • specific functional groups of HA such as carboxyl, hydroxyl and N-acetyl groups
  • chemical reactions such as esterification, acylation, amidation, and sulphation.
  • An example of an esterified-HA is a product sold under the tradename HYAFF 11 (Fidia Advanced Biopolymers, Abano Terme, Italy), which has its carboxyl groups modified with benzyl esters. This material is stable in aqueous media for a few weeks, but completely degrades within 2 months.
  • the scaffold In many tissue repair applications, e.g. muscoloskeletal tissue repair and/or regeneration, the scaffold must be structurally intact for periods far longer than two months. While the use of HA in tissue repair is desired due to HA's function in extracellular matrices and its recognition by certain cell receptors that regulate attachment, proliferation, differentiation and matrix synthesis of certain cell types, thus far approaches using natural HA or known modified-HA have proven inadequate to provide tissue scaffolds that must maintain structural integrity for extended periods of time. A longer lasting material having the appropriate chemical and physical characteristics is necessary in applications such as musculoskeletal tissue repair or regeneration with prolonged enhanced tissue growth capabilities. The HA complexes described herein provide a solution to the need for such tissue scaffolds with such prolonged enhanced capabilities.
  • the present invention is directed to hyaluronic acid complexes that are suitable for incorporation with tissue scaffolds that are suitable for use in repair and/or regeneration of muscoloskeletal tissue and that comprise a biodegradable, porous substrate comprising a biodegradable, hydrophobic polymer.
  • the hyaluronic acid complex is insoluble in water, yet soluble in mixtures of organic and aqueous solvents in which the selected hydrophobic polymer is soluble.
  • FIG. 1 is a scanning electron micrograph (SEM) cross-sectional image of a tissue scaffold utilizing a HA complex of the present invention.
  • FIG. 2 is an SEM cross-sectional image of a tissue scaffold utilizing a HA complex of the present invention.
  • FIG. 3 shows Safranin-O (SO) histological sections (100 ⁇ ) of a tissue scaffold that utilizes a HA complex of the present invention and that includes cultured bovine chondrocytes.
  • SO Safranin-O
  • tissue scaffolds In treatments such as muscoloskeletal tissue repair and/or regeneration, tissue scaffolds must maintain their physical and structural integrity once implanted into the body for extended periods of time, e.g. greater than 2 months, as compared to other treatments, e.g. corneal transplantation, viscosupplementation of the knee, anti-adhesive barriers in spinal surgeries and wound healing applications, where such long-term properties are not required.
  • HA In order to provide such long-term tissue scaffolds with long-term enhanced cell-growth properties, HA must be able to remain incorporated with the scaffold for similarly extended periods of time. HA will dissipate relatively quickly when exposed to fluids of the body when implanted therein. As such, HA is not a successful candidate for use in tissue scaffolds intended for use in applications requiring physical integrity over extended periods of time.
  • this invention utilizes a relatively hydrophobic HA complex, as further described herein, that may be distributed and incorporated on the surfaces of and/or throughout a structurally robust scaffold based on a porous substrate made from biodegradable, hydrophobic polymers.
  • a relatively hydrophobic HA complex includes modified HA that eventually dissolves in water, but at a slower rate than unmodified HA.
  • the modified HA is more compatible with relatively hydrophobic solvents.
  • Relatively hydrophobic solvents are solvents with decreased polarities as compared to water, and include solvents with dielectric constants typically below 60 and above 20, such as, for example, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), acetonitrile, methanol, ethanol, hexamethylphosphoric triamide (HMPT), and acetone.
  • DMSO dimethyl sulfoxide
  • DMF N,N-dimethylformamide
  • HMPT hexamethylphosphoric triamide
  • the hydrophobic HA complexes of the present invention are more compatible with the hydrophobic polymers than unmodified HA or hydrophilic modified HA.
  • the HA complex should be distributed on the surfaces of and/or throughout the porous substrate to obtain optimum cell-growth properties in the tissue scaffold.
  • the HA complex is incorporated with the porous substrate, such that HA complex is bound to the porous substrate and not readily removable from the substrate once implanted in the body.
  • the HA complex can be dissolved in an aqueous/organic solvent mixture and blended with a solution of the hydrophobic polymer in an appropriate organic solvent.
  • the blend of the dissolved HA complex and hydrophobic polymer subsequently can be lyophilized to generate a porous foam tissue scaffold having the HA complex dispersed and incorporated throughout the foam scaffold substrate.
  • the HA complex of the present invention can be dissolved in an organic/aqueous mixture that subsequently can be poured over a hydrophobic substrate, e.g. a fibrous, nonwoven mat, allowed to penetrate the substrate, and then lyophilized to yield a substrate having the HA complex tightly adhered thereto.
  • the HA complex may be applied to one or both of the surface(s) of the scaffold.
  • native HA is a hydrophilic, highly water-soluble material.
  • the HA complex of the present invention is substantially in water at room temperature and shows improved solubility in selected organic solvents and organic/aqueous solvent blends as compared to native HA. It is this characteristic of the HA complex that allows it to be more compatible with hydrophobic polymers as compared to hydrophilic native or modified HA.
  • a macromolecular salt complex of HA was formed via the ion-exchange of a monovalent alkali metal salt of HA, e.g. sodium hyaluronate (HA-Na) or potassium hyaluronate (HA-K) and a tetra alkyl ammonium halide as represented below.
  • a monovalent alkali metal salt of HA e.g. sodium hyaluronate (HA-Na) or potassium hyaluronate (HA-K) and a tetra alkyl ammonium halide as represented below.
  • R is C 8 H 17 to C 18 H 37 and X is Cl or Br.
  • Tetra alkyl ammonium salt complexes of this type can behave as phase transfer catalysts. This reaction occurs by the ion-exchange of the negatively charged carboxylate groups of the monovalent alkali metal salt of HA, with the positively charged tetra alkyl ammonium halides, resulting in the formation of an HA complex with a difference in solubility as compared to unmodified HA.
  • the tetra alkyl ammonium halides used in this invention are soluble in both water and organic solvents, such as alcohols, acetone, 1,4-dioxane and tetrahydrofuran.
  • Tetra alkyl ammonium halides that can be used in this invention include, but are not limited to, tetrabutylammonium bromide, cetyldimethylethylammonium bromide, benzalconium chloride, stearyldimethylbenzylammonium chloride, 3-(benzyldimethylammonio)propanesulfonate, benzyldimethyldecylammonium chloride, benzyldimethyldodecylammonium bromide, benzyldimethyldodecylammonium chloride, benzyldimethylhexadecylammonium chloride, benzyldimethyl(2-hydroxyethyl)ammonium chloride, benzyldimethyltetradecylammonium chloride, and benzethonium chloride.
  • the preferred tetra alkyl ammonium halide is benzalconium chloride (BzCl), a white or yellowish-white solid in the form of an amorphous powder or gelatinous pieces.
  • BzCl benzalconium chloride
  • the chemical scheme for forming a complex between HA-Na and BzCl is shown below.
  • BzCl has been investigated previously as an antimicrobial agent and shown to be safe at concentrations up to 0.1% weight.
  • BzCl is a mixture comprised of alkyldimethylbenzylammonium chlorides.
  • Three major homologues include C 12 , C 14 and C 16 straight chain alkyls. The combination of aliphatic hydrocarbon chains and positively charged ammonium groups imparts facile dissolution in both water and select organic solvents.
  • HA-BzCl complex An added advantage of the HA-BzCl complex is that by changing the ratio of HA to BzC, the solubility of the complex can be changed in a buffered solution.
  • the source of HA-Na can be either animal-derived or obtained by bacterial fermentation.
  • Solvent system for preparation of HA complexes of the present invention include a blend of organic solvents such as 1,4-dioxane, dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMAC)), N,N-dimethylformamide (DMF), and water.
  • DMSO dimethyl sulfoxide
  • DMAC N,N-dimethylacetamide
  • DMF N,N-dimethylformamide
  • the HA complexes formed according to the methods of this invention are not completely soluble in aprotic nonpolar solvents or pure water.
  • the preferred solvent system is a 60/40 blend of -1,4-dioxane/water.
  • the solubility of the HA complex can be varied by changing the ratio of HA-Na to BzCl.
  • Complexes containing 1:1 molar ratios of HA:BzCl ultimately dissolve in aqueous environments slower than complexes comprised of 1:0.5 or 1:0.25. At all of these ratios the complexes are less soluble in an aqueous environment as compared to unmodified HA.
  • the ultimate dissolution of such a complex is primarily through dissociation of HA-Na and BzCl units.
  • the biodegradable, hydrophobic polymer used to prepare the tissue scaffold substrates may be selected from the group consisting of aliphatic polyesters, poly(amino acids), polyalkylene oxalates, polyamides, tyrosine-derived polycarbonates, polyorthoesters, polyoxaesters, poly(anhydrides), polyphosphazenes and biopolymers, e.g. collagen, elastin and bioabsorbable starches and blends thereof. Preferred are the synthetic polymers.
  • aliphatic polyesters are among the preferred synthetic, biodegradable, hydrophobic polymers.
  • Aliphatic polyesters can be homopolymers, copolymers (random, block, segmented, tapered blocks, graft, triblock, etc.) having a linear, branched or star structure.
  • Suitable monomers for making aliphatic homopolymers and copolymers may be selected from the group consisting of, but are not limited to, lactic acid, lactide (including L-, D-, meso and D,L mixtures), glycolic acid, glycolide, epsilon-caprolactone, para-dioxanone (1,4-dioxan-2-one) and trimethylene carbonate (1,3-dioxan-2-one).
  • Synthetic, biodegradable, hydrophobic elastomeric copolymers are also particularly useful in preparing the scaffold substrates.
  • Suitable elastomeric polymers include those with an intrinsic viscosity in the range of 1 dL/g to 4 dl/g, preferably about 1 dL/g to 2 dL/g and most preferably about 1 dL/g to 1.7 dL/g, as determined at 25° C. in a 0.1 gram per deciliter (g/dL) solution of polymer in hexafluoroisopropanol (HFIP).
  • An “elastomeric copolymer” is defined as a polymer which, at room temperature, can be stretched repeatedly to at least twice its original length and which, upon immediate release of stress, will return to approximately its original length.
  • Exemplary synthetic, biodegradable, hydrophobic elastomeric copolymers include, but are not limited to, copolymers of ⁇ -caprolactone (PCL) and glycolide (including polyglycolic acid (PGA)) with a mole ratio of epsilon-caprolactone to glycolide of from about 35/65 to about 65/35, more preferably from 45/55 to 35/65; copolymers of epsilon-caprolactone and lactide (PLA) where the mole ratio of ⁇ -caprolactone to lactide is from about 30/70 to about 95/5 and more preferably from 30/70 to 45/55 or from about 85/15 to about 95/5; copolymers of p-dioxanone (PDS) and lactide where the mole ratio of para-dioxanone to lactide is from about 40/60 to about 60/40; copolymers of epsilon-caprolactone and para-dio
  • the preferred synthetic biodegradable, hydrophobic polymers and copolymers for the present invention are 90/10 PGA/PLA, PDS, 65/35 PGA/PCL, 60/40 PLA/PCL, 85/15 PLA/PCL, 95/5 PLA/PGA and blends thereof.
  • the synthetic biodegradable, hydrophobic polymer can be prepared in the form of a scaffold substrate component by a number of methods known in the art. If fibrous, the synthetic biodegradable, hydrophobic polymer may be extruded into fibers and the fibers then may formed into a porous, fibrous nonwoven structure using standard wet-lay or dry-lay techniques.
  • the synthetic scaffold substrate component can be prepared in the form of a porous, sponge or foam structure by a variety of techniques well known to those having ordinary skill in the art.
  • the hydrophobic polymer may be dissolved in an appropriate solvent for the polymer and then processed into a foam by lyophilization, supercritical solvent foaming, gas injection extrusion, gas injection molding or casting with an extractable material (e.g., salts, sugar or similar suitable materials).
  • the foam substrate component can be made by a polymer-solvent phase separation technique, such as lyophilization.
  • the steps involved in the preparation of these synthetic foams include choosing the appropriate solvents for the polymers to be lyophilized and preparing a homogeneous solution of the polymer in the solution.
  • the polymer-solvent solution then is subjected to a freezing and a vacuum drying cycle.
  • the freezing step phase-separates the solution and the vacuum drying step removes the solvent by sublimation and/or drying, thus leaving a porous polymer structure, or an interconnected, open-cell porous foam.
  • Suitable solvents that may be used in the preparation of the porous foam substrate include, but are not limited to, formic acid, ethyl formate, acetic acid, hexafluoroisopropanol (HFIP), cyclic ethers (e.g., tetrahydrofuran (THF), dimethylene fluoride (DMF), and polydioxanone (PDO)), acetone, methylethyl ketone, dipropyleneglycol methyl ether, 1,4-1,4-dioxane, 1,3-dioxolane, ethylene carbonate, dimethlycarbonate, benzene, toluene, benzyl alcohol, p-xylene, naphthalene, N-methyl pyrrolidone, dimethylformamide, chloroform, 1,2-dichloromethane, dimethylsulfoxide, and mixtures thereof.
  • a preferred solvent is 1,4-diox
  • additional solids may be added to the polymer-solvent system to modify the composition of the resulting foam substrate. As the added particles settle out of solution, the added solids may be more concentrated in desired regions (i.e., near the top, sides or bottom) of the resulting tissue implant, thus causing compositional changes in such regions where desired for a particular purpose.
  • the solids are of a type that will not react with the polymer or the solvent.
  • the added solids have an average diameter of less than about 1 mm and preferably will have an average diameter of from about 50 to about 500 microns.
  • the solids are present in an amount such that they will constitute from about 1 to about 50 volume percent of the total volume of the particle and polymer-solvent mixture (wherein the total volume percent equals 100 volume percent).
  • Exemplary solids include, but are not limited to, particles of demineralized bone, calcium phosphate particles, calcium carbonate particles for bone repair, solids that will render the scaffold radio opaque, leachable solids for pore creation, and particles that are effective as reinforcing materials.
  • Suitable leachable solids include nontoxic leachable materials such as salts, biocompatible mono and disaccharides, polysaccharides, or water soluble proteins.
  • the leachable materials can be removed by immersing the foam substrate with the leachable material in a solvent in which the particle is soluble for a sufficient amount of time to allow leaching of substantially all of the particles, but which does not dissolve or detrimentally alter the foam substrate.
  • Suitable non-bioabsorbable materials include biocompatible metals or bioinert ceramic particles. Further, the non-bioabsorbable materials may include polymers such as polyethylene, polyvinylacetate, polymethylmethacrylate, silicone, polyethylene oxide, polyethylene glycol, polyurethanes, natural biopolymers, and fluorinated polymers and copolymers.
  • effectors including drugs, bioactive molecules or cells, such as platelet rich plasma, bone marrow cells, and a combination of the two, can be added or injected into the tissue scaffold at the point of care.
  • the tissue scaffold may be modified either through physical or chemical means to contain biological or synthetic factors or agents that promote attachment, proliferation, differentiation and matrix synthesis of targeted cell types.
  • the bioactive factors may also comprise part of the scaffold for controlled release of the factor to elicit a desired biological function.
  • Another embodiment would include delivery of small molecules that affect the up regulation of endogenous growth factors.
  • Growth factors, extracellular matrix proteins, and biologically relevant peptide fragments that can be used with the matrices of the current invention include, but are not limited to, antibiotics and antiviral agents; anticancer agents; anti-rejection agents; analgesics and analgesic combinations; anti-inflammatory agents such as acetoaminophen; cytostatic agents such as Rapamycin; hormones such as steroids; analgesics; growth factors, including bone morphogenic proteins (BMP-2, BMP-4, BMP-6, BMP-12, BMP-2); sonic hedgehog; growth differentiation factor (GDF5, GDF6 and GDF8); epidermal growth factor; fibroblast growth factor; platelet derived growth factor (PDGF); insulin like growth factor (IGF-I and IGF-II); transforming growth factors (TGF- ⁇ I–III); parathyroid hormone, vascular endothelial growth factor (VEGF); genetically engineered cells that express desired proteins; and other naturally derived or genetically engineered proteins, polysaccharides,
  • the tissue scaffolds can be seeded or cultured with appropriate cell types prior to implantation.
  • Cells which can be seeded or cultured on the scaffolds include, but are not limited to, bone marrow cells, mesenchymal stem cells, stromal cells, stem cells, embryonic stem cells, chondrocytes, osteoblasts, precursor cells derived from adipose tissue, bone marrow derived progenitor cells, kidney cells, intestinal cells, islets, sertoli cells, peripheral blood progenitor cells, fibroblasts, keratinocytes, nucleus pulposus cells, anulus fibrosis cells, fibrochondrocytes, stem cells isolated from adult tissue, neuronal stem cells, glial cells, macrophages and genetically transformed cells or combination of the above cell.
  • the cells can be seeded on the scaffolds of the present invention for a short period of time, e.g. less than one day, just prior to implantation, or cultured for a longer (>1 day) period, e.g. greater than one day, to allow for cell proliferation and matrix synthesis within the seeded scaffold prior to implantation.
  • the scaffold configuration must be effective to facilitate tissue ingrowth.
  • a preferred tissue ingrowth-promoting configuration is one where the cells of the scaffold are open and of sufficient size to permit cell growth therein.
  • An effective pore size is one in which the pores have an average diameter in the range of from about 20 to about 1,000 microns, more preferably, from about 20 to about 500 microns.
  • This example describes several procedures used to make HA-BzCl complexes.
  • This example describes the stability of the HA-BzCl complex fabricated according to Example 1, in distilled water or aqueous buffer solution.
  • Example 2 250 milligrams of 1:1 HA-BzCl complex made in Example 1 was suspended in 20 grams of distilled water and stirred for 2 weeks at 25° C. The remaining solid was vacuum dried at 40° C. for 48 hours using phosphorous pentoxide drying agent to yield 55 milligram of a white solid. This represents a 78 percent loss of the starting mass of 1:1 HA-BzCl complex.
  • Example 2 72 milligrams of 1:1, 2:1, and 4:1 HA-BzCl complex made in Example 1 were each suspended in PBS solution (pH 7.4, 37° C.) and shaken in a constant temperature water bath. The degradation of the HA-BzCl was monitored by measuring the absorbance peaks corresponding to HA and BzCl at 205 nm and 262 nm, respectively, using a UV/Vis spectrometer. Calibration curves were generated using pure HA and BzCl dissolved in PBS.
  • This example describes the process of incorporating the HA-BzCl complex described in Example 1 into a porous, foam substrate prepared from a hydrophobic polymer.
  • the foam substrate was prepared utilizing a copolymer of 65/35 PGA/PCL produced by Birmingham Polymers Inc. (Birmingham, Ala.) with an I.V. of 1.79 dL/g, as measured in HFIP at 30° C.
  • the foam was fabricated using a lyophilization procedure as described herein.
  • a solution of 0.1 weight percent of HA-BzCl solution in a 60/40 1,4-dioxane/water mixture was prepared.
  • a laboratory scale lyophilizer (Model Duradry, from FTS Kinetics, Stone Ridge, N.Y.), was used in this example.
  • the synthetic foam substrate 70 mm ⁇ 70 mm ⁇ 2 mm
  • the HA-BzCl polymer solution was added to the mold such that the solution covered the foam substrate such that the substrate was submersed in the solution.
  • the mold assembly then was placed on the shelf of the lyophilizer and the freeze-dry sequence begun.
  • the freeze-dry sequence used in this example was: 1) ⁇ 17° C. for 60 minutes; 2) ⁇ 5° C. for 60 minutes under vacuum 100 mT; 3) 5° C. for 120 minutes under vacuum 20 mT; 4) 20° C. for 120 minutes under vacuum 20 mT.
  • the mold assembly was removed from the lyophilizer and allowed to degas in a vacuum hood for 2 to 3 hours.
  • the tissue scaffold comprising the substrate and the incorporated Ha-BZ was taken from the mold and stored under nitrogen.
  • FIG. 1 is a scanning electron micrograph (SEM) of a cross-section of the foam tissue scaffold.
  • SEM scanning electron micrograph
  • This example describes the process of incorporating the HA-BzCl complex described in Example 1 within a synthetic, porous, nonwoven substrate.
  • the laboratory scale lyophilizer from Example 4 was used in this example.
  • Three sheets of a synthetic nonwoven substrate (70 mm ⁇ 70 mm ⁇ 2 mm) composed of 90/10 PGA/PCL fibers were prepared and placed in 4-inch ⁇ 4-inch aluminum molds.
  • Three solutions of HA-BzCl in 60/40 1,4-dioxane/water mixture were prepared with 0.05, 0.10, and 0.25 weight percent HA-BzCl, respectively. The three solutions were added to the three molds such that the substrates were immersed in the solutions.
  • the mold assemblies were placed on the shelf of the lyophilizer and the freeze-dry sequence begun.
  • the freeze-dry sequence used in this example was the same as used in Example 4.
  • the mold assemblies were removed from the lyophilizer and allowed to degas in a vacuum hood for 2 to 3 hours.
  • the tissue scaffolds were taken from the mold and stored under nitrogen.
  • FIG. 2 is a scanning electron micrograph (SEM) of a cross-section of the nonwoven tissue scaffold.
  • SEM scanning electron micrograph
  • This example illustrates that chondrocytes proliferate and synthesize a proteoglycan-rich matrix within the tissue scaffolds described in Example 4.
  • the 90/10 PGA/PCL nonwoven scaffolds comprising 0.05, 0.1, and 0.25 weight percent HA-BzCl complex in a 60:40 1,4-dioxane/water mixture from Example 5 were evaluated for chondrocyte response.
  • Bovine chondrocytes were isolated from bovine shoulders as described by Buschmann, et al., in J. Orthop. Res., 10, 745, (1992). Bovine chondrocytes were cultured in Dulbecco's modified eagles medium (DMEM-high glucose) supplemented with 10% fetal calf serum (FCS), 10 mM HEPES, 0.1 mM nonessential amino acids, 20 mg/ml L-proline, 50 mg/ml ascorbic acid, 100 U/ml penicillin, 100 mg/ml streptomycin and 0.25 mg/ml amphotericin B (growth media). Half of the medium was replenished every other day.
  • DMEM-high glucose Dulbecco's modified eagles medium
  • FCS fetal calf serum
  • HEPES fetal calf serum
  • nonessential amino acids 20 mg/ml L-proline
  • 50 mg/ml ascorbic acid 100 U/ml
  • tissue scaffolds cut to 5 mm in diameter and 1.5 mm thick, were sterilized for 20 minutes in 70 percent ethanol, followed by five rinses of phosphate-buffered saline (PBS).
  • PBS phosphate-buffered saline
  • Freshly isolated bovine chondrocytes were seeded at a density of 5 ⁇ 10 6 cells/scaffold in 24 well low cluster dishes, by adding a cell suspension (15 ml) onto each scaffold. Cells were allowed to attach to the scaffold for three hours before addition of 1.5 ml of medium. Scaffolds were cultured for up to 1 week in a humidified incubator at 37° C. in an atmosphere of 5 percent CO 2 and 95 percent air. Half of the medium was replaced every other day.
  • FIG. 3 shows SO histological sections (100 ⁇ ) of the 0.05 and 0.1 weight percent HA-BzCl-impregnated nonwoven tissue scaffolds cultured with bovine chondrocytes for 1 week.
  • the figures show cell attachment, proliferation, and matrix formation in each of the scaffolds.
  • This example describes the process of forming a porous, foam tissue scaffold from a solution comprising a blend of HA-BzCl (1:1 molar ratio) complex with a synthetic, biodegradable, hydrophobic polymer.
  • a solution of 0.10 weight percent of HA-BzCl (1:1) solution in a 60/40 1,4-dioxane/water mixture was prepared and mixed in a 1:9 volume ratio with a 5% 65/35 PGA/PCL solution in 1,4-dioxane, poured into an aluminum mold and immediately placed over a liquid nitrogen bath for 5 minutes to freeze the solution.
  • the mold was transferred to a laboratory scale lyophilizer and lyophilized according to the protocol outlined in Example 4.
  • the mold assembly was removed from the lyophilizer and allowed to degas in a vacuum hood for 2 to 3 hours.
  • the scaffold was taken from the mold and stored under nitrogen.

Abstract

The present invention includes hyaluronic acid complexes of a monovalent alkali metal salt of hyaluronic acid and a tetra alkyl ammonium halide that are suitable for incorporation with tissue scaffolds that are suitable for use in repair and/or regeneration of muscoloskeletal tissue and that include a biodegradable, porous substrate made from a biodegradable, hydrophobic polymer, where the hyaluronic acid complex is substantially insoluble in water at room temperature, yet soluble in mixtures of organic and aqueous solvents in which the selected hydrophobic polymer is soluble.

Description

FIELD OF THE INVENTION
The present invention is directed to hyaluronic acid complexes suitable for incorporation with tissue scaffolds that are suitable for use in muscoloskeletal tissue repair and/or regeneration.
BACKGROUND OF THE INVENTION
There is a clinical need for biocompatible and biodegradable structural matrices that facilitate tissue infiltration to repair/regenerate diseased or damaged tissue. Previous attempts have used a number of naturally occurring, as well as synthetic biodegradable materials as scaffolds in the tissue repair process.
One class of biodegradable and biocompatible materials is the family of polysaccharides. One particular polysaccharide used for scaffolds is hyaluronic acid (HA). HA is a naturally-occurring linear polysaccharide comprised of D-glucuronic acid and N-acetyl-D-glucosamine. The ionic polymer has a range of molecular weight of from 1,000–10,000,000 Daltons. The use of purified HA has become common practice for treatments such as corneal transplantation, viscosupplementation of the knee, anti-adhesive barriers in spinal surgeries and wound healing applications.
HA has been explored as a scaffold to enhance the repair of tissue. However, the poor physical properties of natural HA and its rapid resorption by the body has restricted its use to applications where a structurally sound scaffold is not required.
Numerous groups have attempted to modify HA to obtain a more robust and water insoluble biopolymer for tissue engineering applications. One line of modifications involved the use of cross-linking agents. These cross-linking agents include formaldehyde, glutaraldehyde, vinyl sulphone, biscarbodiimides, poly-functional epoxides, glycidyl ether, photocurable cinnamic acid derivatives and adipic dihydrazide. However, there are concerns regarding the potential toxicity of some of the cross-linking agents.
HA derivatives have been obtained by targeting specific functional groups of HA, such as carboxyl, hydroxyl and N-acetyl groups through chemical reactions, such as esterification, acylation, amidation, and sulphation. An example of an esterified-HA is a product sold under the tradename HYAFF 11 (Fidia Advanced Biopolymers, Abano Terme, Italy), which has its carboxyl groups modified with benzyl esters. This material is stable in aqueous media for a few weeks, but completely degrades within 2 months.
In many tissue repair applications, e.g. muscoloskeletal tissue repair and/or regeneration, the scaffold must be structurally intact for periods far longer than two months. While the use of HA in tissue repair is desired due to HA's function in extracellular matrices and its recognition by certain cell receptors that regulate attachment, proliferation, differentiation and matrix synthesis of certain cell types, thus far approaches using natural HA or known modified-HA have proven inadequate to provide tissue scaffolds that must maintain structural integrity for extended periods of time. A longer lasting material having the appropriate chemical and physical characteristics is necessary in applications such as musculoskeletal tissue repair or regeneration with prolonged enhanced tissue growth capabilities. The HA complexes described herein provide a solution to the need for such tissue scaffolds with such prolonged enhanced capabilities.
SUMMARY OF THE INVENTION
The present invention is directed to hyaluronic acid complexes that are suitable for incorporation with tissue scaffolds that are suitable for use in repair and/or regeneration of muscoloskeletal tissue and that comprise a biodegradable, porous substrate comprising a biodegradable, hydrophobic polymer. The hyaluronic acid complex is insoluble in water, yet soluble in mixtures of organic and aqueous solvents in which the selected hydrophobic polymer is soluble.
BRIEF DESCRIPTION OF THE FIGURES
FIG. 1 is a scanning electron micrograph (SEM) cross-sectional image of a tissue scaffold utilizing a HA complex of the present invention.
FIG. 2 is an SEM cross-sectional image of a tissue scaffold utilizing a HA complex of the present invention.
FIG. 3 shows Safranin-O (SO) histological sections (100×) of a tissue scaffold that utilizes a HA complex of the present invention and that includes cultured bovine chondrocytes.
 DETAILED DESCRIPTION OF THE INVENTION
In treatments such as muscoloskeletal tissue repair and/or regeneration, tissue scaffolds must maintain their physical and structural integrity once implanted into the body for extended periods of time, e.g. greater than 2 months, as compared to other treatments, e.g. corneal transplantation, viscosupplementation of the knee, anti-adhesive barriers in spinal surgeries and wound healing applications, where such long-term properties are not required. In order to provide such long-term tissue scaffolds with long-term enhanced cell-growth properties, HA must be able to remain incorporated with the scaffold for similarly extended periods of time. HA will dissipate relatively quickly when exposed to fluids of the body when implanted therein. As such, HA is not a successful candidate for use in tissue scaffolds intended for use in applications requiring physical integrity over extended periods of time.
In order to circumvent the shortcomings of tissue scaffolds using unmodified HA or hydrophilic modified HA, this invention utilizes a relatively hydrophobic HA complex, as further described herein, that may be distributed and incorporated on the surfaces of and/or throughout a structurally robust scaffold based on a porous substrate made from biodegradable, hydrophobic polymers. As used herein, the term “relatively hydrophobic” includes modified HA that eventually dissolves in water, but at a slower rate than unmodified HA. Furthermore, because of its relatively hydrophobic nature, the modified HA is more compatible with relatively hydrophobic solvents. Relatively hydrophobic solvents are solvents with decreased polarities as compared to water, and include solvents with dielectric constants typically below 60 and above 20, such as, for example, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), acetonitrile, methanol, ethanol, hexamethylphosphoric triamide (HMPT), and acetone. The hydrophobic HA complexes of the present invention are more compatible with the hydrophobic polymers than unmodified HA or hydrophilic modified HA.
As will be noted herein, the HA complex should be distributed on the surfaces of and/or throughout the porous substrate to obtain optimum cell-growth properties in the tissue scaffold. In addition, the HA complex is incorporated with the porous substrate, such that HA complex is bound to the porous substrate and not readily removable from the substrate once implanted in the body.
In one embodiment, the HA complex can be dissolved in an aqueous/organic solvent mixture and blended with a solution of the hydrophobic polymer in an appropriate organic solvent. The blend of the dissolved HA complex and hydrophobic polymer subsequently can be lyophilized to generate a porous foam tissue scaffold having the HA complex dispersed and incorporated throughout the foam scaffold substrate. Alternatively, the HA complex of the present invention can be dissolved in an organic/aqueous mixture that subsequently can be poured over a hydrophobic substrate, e.g. a fibrous, nonwoven mat, allowed to penetrate the substrate, and then lyophilized to yield a substrate having the HA complex tightly adhered thereto. Alternately, the HA complex may be applied to one or both of the surface(s) of the scaffold.
As noted above, native HA is a hydrophilic, highly water-soluble material. The HA complex of the present invention is substantially in water at room temperature and shows improved solubility in selected organic solvents and organic/aqueous solvent blends as compared to native HA. It is this characteristic of the HA complex that allows it to be more compatible with hydrophobic polymers as compared to hydrophilic native or modified HA.
To prepare HA complexes of the present invention, a macromolecular salt complex of HA was formed via the ion-exchange of a monovalent alkali metal salt of HA, e.g. sodium hyaluronate (HA-Na) or potassium hyaluronate (HA-K) and a tetra alkyl ammonium halide as represented below.
Figure US07091191-20060815-C00001
where R is C8H17 to C18H37 and X is Cl or Br.
Tetra alkyl ammonium salt complexes of this type can behave as phase transfer catalysts. This reaction occurs by the ion-exchange of the negatively charged carboxylate groups of the monovalent alkali metal salt of HA, with the positively charged tetra alkyl ammonium halides, resulting in the formation of an HA complex with a difference in solubility as compared to unmodified HA. The tetra alkyl ammonium halides used in this invention are soluble in both water and organic solvents, such as alcohols, acetone, 1,4-dioxane and tetrahydrofuran.
Tetra alkyl ammonium halides that can be used in this invention include, but are not limited to, tetrabutylammonium bromide, cetyldimethylethylammonium bromide, benzalconium chloride, stearyldimethylbenzylammonium chloride, 3-(benzyldimethylammonio)propanesulfonate, benzyldimethyldecylammonium chloride, benzyldimethyldodecylammonium bromide, benzyldimethyldodecylammonium chloride, benzyldimethylhexadecylammonium chloride, benzyldimethyl(2-hydroxyethyl)ammonium chloride, benzyldimethyltetradecylammonium chloride, and benzethonium chloride.
The preferred tetra alkyl ammonium halide is benzalconium chloride (BzCl), a white or yellowish-white solid in the form of an amorphous powder or gelatinous pieces. The chemical scheme for forming a complex between HA-Na and BzCl is shown below.
Figure US07091191-20060815-C00002
BzCl has been investigated previously as an antimicrobial agent and shown to be safe at concentrations up to 0.1% weight. BzCl is a mixture comprised of alkyldimethylbenzylammonium chlorides. Three major homologues include C12, C14 and C16 straight chain alkyls. The combination of aliphatic hydrocarbon chains and positively charged ammonium groups imparts facile dissolution in both water and select organic solvents.
An added advantage of the HA-BzCl complex is that by changing the ratio of HA to BzC, the solubility of the complex can be changed in a buffered solution.
The source of HA-Na can be either animal-derived or obtained by bacterial fermentation. Solvent system for preparation of HA complexes of the present invention include a blend of organic solvents such as 1,4-dioxane, dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMAC)), N,N-dimethylformamide (DMF), and water. The HA complexes formed according to the methods of this invention are not completely soluble in aprotic nonpolar solvents or pure water.
The preferred solvent system is a 60/40 blend of -1,4-dioxane/water. The solubility of the HA complex can be varied by changing the ratio of HA-Na to BzCl. Complexes containing 1:1 molar ratios of HA:BzCl ultimately dissolve in aqueous environments slower than complexes comprised of 1:0.5 or 1:0.25. At all of these ratios the complexes are less soluble in an aqueous environment as compared to unmodified HA. The ultimate dissolution of such a complex is primarily through dissociation of HA-Na and BzCl units. By using methods described herein, one skilled in art can appreciate that the dissolution rate of the HA complex of the present invention can be tailored to match the kinetics of tissue repair.
The biodegradable, hydrophobic polymer used to prepare the tissue scaffold substrates may be selected from the group consisting of aliphatic polyesters, poly(amino acids), polyalkylene oxalates, polyamides, tyrosine-derived polycarbonates, polyorthoesters, polyoxaesters, poly(anhydrides), polyphosphazenes and biopolymers, e.g. collagen, elastin and bioabsorbable starches and blends thereof. Preferred are the synthetic polymers.
Currently, aliphatic polyesters are among the preferred synthetic, biodegradable, hydrophobic polymers. Aliphatic polyesters can be homopolymers, copolymers (random, block, segmented, tapered blocks, graft, triblock, etc.) having a linear, branched or star structure. Suitable monomers for making aliphatic homopolymers and copolymers may be selected from the group consisting of, but are not limited to, lactic acid, lactide (including L-, D-, meso and D,L mixtures), glycolic acid, glycolide, epsilon-caprolactone, para-dioxanone (1,4-dioxan-2-one) and trimethylene carbonate (1,3-dioxan-2-one).
Synthetic, biodegradable, hydrophobic elastomeric copolymers are also particularly useful in preparing the scaffold substrates. Suitable elastomeric polymers include those with an intrinsic viscosity in the range of 1 dL/g to 4 dl/g, preferably about 1 dL/g to 2 dL/g and most preferably about 1 dL/g to 1.7 dL/g, as determined at 25° C. in a 0.1 gram per deciliter (g/dL) solution of polymer in hexafluoroisopropanol (HFIP). An “elastomeric copolymer” is defined as a polymer which, at room temperature, can be stretched repeatedly to at least twice its original length and which, upon immediate release of stress, will return to approximately its original length.
Exemplary synthetic, biodegradable, hydrophobic elastomeric copolymers include, but are not limited to, copolymers of ε-caprolactone (PCL) and glycolide (including polyglycolic acid (PGA)) with a mole ratio of epsilon-caprolactone to glycolide of from about 35/65 to about 65/35, more preferably from 45/55 to 35/65; copolymers of epsilon-caprolactone and lactide (PLA) where the mole ratio of ε-caprolactone to lactide is from about 30/70 to about 95/5 and more preferably from 30/70 to 45/55 or from about 85/15 to about 95/5; copolymers of p-dioxanone (PDS) and lactide where the mole ratio of para-dioxanone to lactide is from about 40/60 to about 60/40; copolymers of epsilon-caprolactone and para-dioxanone where the mole ratio of epsilon-caprolactone to para-dioxanone is from about 30/70 to about 70/30; and blends thereof.
The preferred synthetic biodegradable, hydrophobic polymers and copolymers for the present invention are 90/10 PGA/PLA, PDS, 65/35 PGA/PCL, 60/40 PLA/PCL, 85/15 PLA/PCL, 95/5 PLA/PGA and blends thereof.
The synthetic biodegradable, hydrophobic polymer can be prepared in the form of a scaffold substrate component by a number of methods known in the art. If fibrous, the synthetic biodegradable, hydrophobic polymer may be extruded into fibers and the fibers then may formed into a porous, fibrous nonwoven structure using standard wet-lay or dry-lay techniques.
Alternatively, the synthetic scaffold substrate component can be prepared in the form of a porous, sponge or foam structure by a variety of techniques well known to those having ordinary skill in the art. For example, the hydrophobic polymer may be dissolved in an appropriate solvent for the polymer and then processed into a foam by lyophilization, supercritical solvent foaming, gas injection extrusion, gas injection molding or casting with an extractable material (e.g., salts, sugar or similar suitable materials).
In one embodiment, the foam substrate component can be made by a polymer-solvent phase separation technique, such as lyophilization.
The steps involved in the preparation of these synthetic foams include choosing the appropriate solvents for the polymers to be lyophilized and preparing a homogeneous solution of the polymer in the solution. The polymer-solvent solution then is subjected to a freezing and a vacuum drying cycle. The freezing step phase-separates the solution and the vacuum drying step removes the solvent by sublimation and/or drying, thus leaving a porous polymer structure, or an interconnected, open-cell porous foam.
Suitable solvents that may be used in the preparation of the porous foam substrate include, but are not limited to, formic acid, ethyl formate, acetic acid, hexafluoroisopropanol (HFIP), cyclic ethers (e.g., tetrahydrofuran (THF), dimethylene fluoride (DMF), and polydioxanone (PDO)), acetone, methylethyl ketone, dipropyleneglycol methyl ether, 1,4-1,4-dioxane, 1,3-dioxolane, ethylene carbonate, dimethlycarbonate, benzene, toluene, benzyl alcohol, p-xylene, naphthalene, N-methyl pyrrolidone, dimethylformamide, chloroform, 1,2-dichloromethane, dimethylsulfoxide, and mixtures thereof. Among these solvents utilized, a preferred solvent is 1,4-dioxane. A homogeneous solution of the polymer in the solvent is prepared using standard techniques.
In one embodiment, additional solids may be added to the polymer-solvent system to modify the composition of the resulting foam substrate. As the added particles settle out of solution, the added solids may be more concentrated in desired regions (i.e., near the top, sides or bottom) of the resulting tissue implant, thus causing compositional changes in such regions where desired for a particular purpose.
A variety of types of solids can be added to the polymer-solvent system. Preferably, the solids are of a type that will not react with the polymer or the solvent. Generally, the added solids have an average diameter of less than about 1 mm and preferably will have an average diameter of from about 50 to about 500 microns. When utilized, preferably the solids are present in an amount such that they will constitute from about 1 to about 50 volume percent of the total volume of the particle and polymer-solvent mixture (wherein the total volume percent equals 100 volume percent).
Exemplary solids include, but are not limited to, particles of demineralized bone, calcium phosphate particles, calcium carbonate particles for bone repair, solids that will render the scaffold radio opaque, leachable solids for pore creation, and particles that are effective as reinforcing materials.
Suitable leachable solids include nontoxic leachable materials such as salts, biocompatible mono and disaccharides, polysaccharides, or water soluble proteins. The leachable materials can be removed by immersing the foam substrate with the leachable material in a solvent in which the particle is soluble for a sufficient amount of time to allow leaching of substantially all of the particles, but which does not dissolve or detrimentally alter the foam substrate.
Suitable non-bioabsorbable materials include biocompatible metals or bioinert ceramic particles. Further, the non-bioabsorbable materials may include polymers such as polyethylene, polyvinylacetate, polymethylmethacrylate, silicone, polyethylene oxide, polyethylene glycol, polyurethanes, natural biopolymers, and fluorinated polymers and copolymers.
In addition, effectors, including drugs, bioactive molecules or cells, such as platelet rich plasma, bone marrow cells, and a combination of the two, can be added or injected into the tissue scaffold at the point of care.
The tissue scaffold may be modified either through physical or chemical means to contain biological or synthetic factors or agents that promote attachment, proliferation, differentiation and matrix synthesis of targeted cell types. Furthermore, the bioactive factors may also comprise part of the scaffold for controlled release of the factor to elicit a desired biological function. Another embodiment would include delivery of small molecules that affect the up regulation of endogenous growth factors. Growth factors, extracellular matrix proteins, and biologically relevant peptide fragments that can be used with the matrices of the current invention include, but are not limited to, antibiotics and antiviral agents; anticancer agents; anti-rejection agents; analgesics and analgesic combinations; anti-inflammatory agents such as acetoaminophen; cytostatic agents such as Rapamycin; hormones such as steroids; analgesics; growth factors, including bone morphogenic proteins (BMP-2, BMP-4, BMP-6, BMP-12, BMP-2); sonic hedgehog; growth differentiation factor (GDF5, GDF6 and GDF8); epidermal growth factor; fibroblast growth factor; platelet derived growth factor (PDGF); insulin like growth factor (IGF-I and IGF-II); transforming growth factors (TGF-β I–III); parathyroid hormone, vascular endothelial growth factor (VEGF); genetically engineered cells that express desired proteins; and other naturally derived or genetically engineered proteins, polysaccharides, glycoproteins, or lipoproteins. The biological factors may be obtained either through a commercial source or isolated and purified from a tissue.
The tissue scaffolds can be seeded or cultured with appropriate cell types prior to implantation. Cells which can be seeded or cultured on the scaffolds include, but are not limited to, bone marrow cells, mesenchymal stem cells, stromal cells, stem cells, embryonic stem cells, chondrocytes, osteoblasts, precursor cells derived from adipose tissue, bone marrow derived progenitor cells, kidney cells, intestinal cells, islets, sertoli cells, peripheral blood progenitor cells, fibroblasts, keratinocytes, nucleus pulposus cells, anulus fibrosis cells, fibrochondrocytes, stem cells isolated from adult tissue, neuronal stem cells, glial cells, macrophages and genetically transformed cells or combination of the above cell. The cells can be seeded on the scaffolds of the present invention for a short period of time, e.g. less than one day, just prior to implantation, or cultured for a longer (>1 day) period, e.g. greater than one day, to allow for cell proliferation and matrix synthesis within the seeded scaffold prior to implantation.
The scaffold configuration must be effective to facilitate tissue ingrowth. A preferred tissue ingrowth-promoting configuration is one where the cells of the scaffold are open and of sufficient size to permit cell growth therein. An effective pore size is one in which the pores have an average diameter in the range of from about 20 to about 1,000 microns, more preferably, from about 20 to about 500 microns.
The following examples are illustrative of the principles and practice of the invention, although not intended to limit the scope of the invention. Numerous additional embodiments within the scope and spirit of the invention will become apparent to those skilled in the art.
EXAMPLE 1
This example describes several procedures used to make HA-BzCl complexes.
Equimolar amounts of sodium hyaluronate (1.5 gm) and benzalconium chloride (1.3 gm) were mixed together in distilled water. After 1 hour of stirring at 25° C., the precipitated solid was filtered and vacuum dried overnight, yielding 1:1 molar HA-BzCl complex.
In a similar manner, 2:1 and 4:1 molar HA-BzCl complexes were made, except the amount of benzalconium chloride was changed from (1.3 gm) for the 1:1 molar HA-BzCl complex, to 0.65 gm and 0.33 gm of benzalconium chloride for the 2:1 and 4:1 molar HA-BzCl complexes, respectively.
An alternate procedure to form 1:1 HA-BzCl complex was also used. Sodium hyaluronate (1.5 gm) was added to a solution containing benzalconium chloride (1.3 gm) in a mixture of 1,4-dioxane (118 gm) and water (78.5 gm). The solution was stirred for 24 hours at 25° C. and centrifuged for 1 hour at a rate of 4,000 rpm using an Eppendorf Centrifuge 5810R. Residual NaCl was removed by dialysis. Dialysis times varied and were generally less than 4 hours to minimize loss of benzalconium groups.
EXAMPLE 2
This example describes the stability of the HA-BzCl complex fabricated according to Example 1, in distilled water or aqueous buffer solution.
First, 250 milligrams of 1:1 HA-BzCl complex made in Example 1 was suspended in 20 grams of distilled water and stirred for 2 weeks at 25° C. The remaining solid was vacuum dried at 40° C. for 48 hours using phosphorous pentoxide drying agent to yield 55 milligram of a white solid. This represents a 78 percent loss of the starting mass of 1:1 HA-BzCl complex.
In a second experiment, 72 milligrams of 1:1, 2:1, and 4:1 HA-BzCl complex made in Example 1 were each suspended in PBS solution (pH 7.4, 37° C.) and shaken in a constant temperature water bath. The degradation of the HA-BzCl was monitored by measuring the absorbance peaks corresponding to HA and BzCl at 205 nm and 262 nm, respectively, using a UV/Vis spectrometer. Calibration curves were generated using pure HA and BzCl dissolved in PBS. The results indicated that 100 percent of the 4:1 HA-BzCl degraded after 1 day, 100 percent of the 2:1 HA-BzCl complex degraded after 4 days, and 70 percent of the 1:1 HA-BzCl complex degraded after 2 weeks.
EXAMPLE 3
This example describes the process of incorporating the HA-BzCl complex described in Example 1 into a porous, foam substrate prepared from a hydrophobic polymer. The foam substrate was prepared utilizing a copolymer of 65/35 PGA/PCL produced by Birmingham Polymers Inc. (Birmingham, Ala.) with an I.V. of 1.79 dL/g, as measured in HFIP at 30° C. The foam was fabricated using a lyophilization procedure as described herein.
A solution of 0.1 weight percent of HA-BzCl solution in a 60/40 1,4-dioxane/water mixture was prepared.
A laboratory scale lyophilizer (Model Duradry, from FTS Kinetics, Stone Ridge, N.Y.), was used in this example. The synthetic foam substrate (70 mm×70 mm×2 mm) composed of 65/35 PGA/PCL was placed in a 4-inch×4-inch aluminum mold. The HA-BzCl polymer solution was added to the mold such that the solution covered the foam substrate such that the substrate was submersed in the solution.
The mold assembly then was placed on the shelf of the lyophilizer and the freeze-dry sequence begun. The freeze-dry sequence used in this example was: 1) −17° C. for 60 minutes; 2) −5° C. for 60 minutes under vacuum 100 mT; 3) 5° C. for 120 minutes under vacuum 20 mT; 4) 20° C. for 120 minutes under vacuum 20 mT.
After the cycle was completed, the mold assembly was removed from the lyophilizer and allowed to degas in a vacuum hood for 2 to 3 hours. The tissue scaffold comprising the substrate and the incorporated Ha-BZ was taken from the mold and stored under nitrogen.
FIG. 1 is a scanning electron micrograph (SEM) of a cross-section of the foam tissue scaffold. The SEM shows the lyophilized HA-BzCl 5 incorporated within and dispersed throughout the foam tissue scaffold substrate 10.
EXAMPLE 5
This example describes the process of incorporating the HA-BzCl complex described in Example 1 within a synthetic, porous, nonwoven substrate. The laboratory scale lyophilizer from Example 4 was used in this example. Three sheets of a synthetic nonwoven substrate (70 mm×70 mm×2 mm) composed of 90/10 PGA/PCL fibers were prepared and placed in 4-inch×4-inch aluminum molds. Three solutions of HA-BzCl in 60/40 1,4-dioxane/water mixture were prepared with 0.05, 0.10, and 0.25 weight percent HA-BzCl, respectively. The three solutions were added to the three molds such that the substrates were immersed in the solutions.
The mold assemblies were placed on the shelf of the lyophilizer and the freeze-dry sequence begun. The freeze-dry sequence used in this example was the same as used in Example 4.
After the cycle was completed, the mold assemblies were removed from the lyophilizer and allowed to degas in a vacuum hood for 2 to 3 hours. The tissue scaffolds were taken from the mold and stored under nitrogen.
The resulting tissue scaffolds contained the nonwoven substrate having the HA-BzCl dispersed there through. FIG. 2 is a scanning electron micrograph (SEM) of a cross-section of the nonwoven tissue scaffold. The SEM clearly shows the lyophilized Ha-BzCl 15 incorporated with the synthetic fibers 20 of the nonwoven substrate.
EXAMPLE 5
This example illustrates that chondrocytes proliferate and synthesize a proteoglycan-rich matrix within the tissue scaffolds described in Example 4. Specifically, the 90/10 PGA/PCL nonwoven scaffolds comprising 0.05, 0.1, and 0.25 weight percent HA-BzCl complex in a 60:40 1,4-dioxane/water mixture from Example 5 were evaluated for chondrocyte response.
Primary chondrocytes were isolated from bovine shoulders as described by Buschmann, et al., in J. Orthop. Res., 10, 745, (1992). Bovine chondrocytes were cultured in Dulbecco's modified eagles medium (DMEM-high glucose) supplemented with 10% fetal calf serum (FCS), 10 mM HEPES, 0.1 mM nonessential amino acids, 20 mg/ml L-proline, 50 mg/ml ascorbic acid, 100 U/ml penicillin, 100 mg/ml streptomycin and 0.25 mg/ml amphotericin B (growth media). Half of the medium was replenished every other day.
The tissue scaffolds, cut to 5 mm in diameter and 1.5 mm thick, were sterilized for 20 minutes in 70 percent ethanol, followed by five rinses of phosphate-buffered saline (PBS).
Freshly isolated bovine chondrocytes were seeded at a density of 5×106 cells/scaffold in 24 well low cluster dishes, by adding a cell suspension (15 ml) onto each scaffold. Cells were allowed to attach to the scaffold for three hours before addition of 1.5 ml of medium. Scaffolds were cultured for up to 1 week in a humidified incubator at 37° C. in an atmosphere of 5 percent CO2 and 95 percent air. Half of the medium was replaced every other day.
Scaffolds were harvested at 1 and 7 days, and evaluated for histological staining. At each time point, three samples were fixed in 10 percent buffered formalin, embedded in paraffin and sectioned using a Zeiss Microtome. Cell distribution within tissue scaffolds was assessed by hematoxylin staining of cross sections of scaffolds 24 hours after cell seeding. Furthermore, sections were also stained for the presence of sulfated proteoglycans Safranin-O (SO; sulfated GAG's). Computer images were acquired using a Nikon Microphot-FXA microscope fitted with a Nikon CCD video camera (Nikon, Japan).
FIG. 3 shows SO histological sections (100×) of the 0.05 and 0.1 weight percent HA-BzCl-impregnated nonwoven tissue scaffolds cultured with bovine chondrocytes for 1 week. The figures show cell attachment, proliferation, and matrix formation in each of the scaffolds.
EXAMPLE 6
This example describes the process of forming a porous, foam tissue scaffold from a solution comprising a blend of HA-BzCl (1:1 molar ratio) complex with a synthetic, biodegradable, hydrophobic polymer.
A solution of 0.10 weight percent of HA-BzCl (1:1) solution in a 60/40 1,4-dioxane/water mixture was prepared and mixed in a 1:9 volume ratio with a 5% 65/35 PGA/PCL solution in 1,4-dioxane, poured into an aluminum mold and immediately placed over a liquid nitrogen bath for 5 minutes to freeze the solution. The mold was transferred to a laboratory scale lyophilizer and lyophilized according to the protocol outlined in Example 4.
After the cycle was completed, the mold assembly was removed from the lyophilizer and allowed to degas in a vacuum hood for 2 to 3 hours. The scaffold was taken from the mold and stored under nitrogen.
The following tables represent the relative solubility behavior of Ha-Bz complexes prepared according to the invention in mixtures of 1,4-dioxane/water and DMAC/water, respectively.
TABLE 1
Room Temperature Solubility of HA:BzCl in 1,4-dioxane/water.
HA:BzCl HA:BzCl 1,4-dioxane/H2O Ha:BzCl
Mole Ratio Weight % (w/w) Solubility
1:1 1  0/100 No
1:1 0.5  0/100 No
1:1 0.25  0/100 No
1:1 1 50/50 Yes
1:1 1 70/30 No
1:1 1 65/35 Partially
1:1 0.5 70/30 No
1:1 0.5 65/35 Partially
1:1 0.5 60/40 Yes
1:1 0.5 50/50 Yes
1:1 0.25 50/50 Yes
1:1 1 75/25 No
1:1 0.5 75/25 No
1:1 0.25 75/25 No
1:1 0.25 100/0  No
1:0.5 1  0/100 No
1:0.5 0.5  0/100 No
1:0.5 0.25  0/100 No
1:0.5 1 50/50 Yes
1:0.5 0.5 50/50 Yes
1:0.5 0.25 50/50 Yes
1:0.5 1 75/25 No
1:0.5 0.5 75/25 No
1:0.5 0.25 75/25 No
1:0.5 0.25 100/0  No
HA = sodium hyaluronate derived from bacterial fermentation (~450 000 Da)
BzCl = benzalconium chloride
TABLE 2
Room Temperature Solubility of HA:BzCl in DMAC/H2O.
HA:BzCl HA:BzCl
Mole Ratio HA:BzCl % DMAC/H2O (w/w) Solubility
1:1 1 25/75 No
1:1 0.5 25/75 No
1:1 0.25 25/75 No
1:1 0.25 100/0  No
2:1 1 100/0  No
2:1 0.5 100/0  No
2:1 0.25 100/0  No
2:1 1 60/40 Yes
2:1 1 50/50 Yes
2:1 0.5 50/50 Yes
2:1 0.25 50/50 Yes
2:1 1 25/75 No
2:1 0.5 25/75 No
2:1 0.25 25/75 No
2:1 0.25  0/100 No
HA = sodium hyaluronate derived from bacterial fermentation (~450 000 Da)
BzCl = benzalconium chloride

Claims (6)

1. A hyaluronic acid complex suitable for incorporation with tissue scaffolds comprising a hydrophobic polymer and that are suitable for use in repair and/or regeneration of muscoloskeletal tissue, said hyaluronic acid complex comprising a complex of a monovalent alkali metal salt of hyaluronic acid and a tetra alkyl ammonium halide represented by the formula:
Figure US07091191-20060815-C00003
where R is C8H17 to C18H37 and X is Cl or Br,
wherein said hyaluronic acid complex is substantially insoluble in water at room temperature, yet soluble in mixtures of organic and aqueous solvents in which said hydrophobic polymer is soluble.
2. The hyaluronic acid complex of claim 1 wherein said monovalent alkali metal salt is selected from the group consisting of sodium hyaluronate and potassium hyaluronate.
3. The hyaluronic acid complex of claim 2 wherein the molar ratio of sodium hyaluronate to tetra alkyl ammonium halide is between about 10:1 and about 1:10.
4. The hyaluronic acid complex of claim 3 wherein said tetra alkyl ammonium halide is selected from the group consisting of tetrabutylammonium bromide, cetyldimethylethylammonium bromide, benzalconium chloride, stearyldimethylbenzylammonium chloride, 3-(benzyldimethylammonio)propanesulfonate, benzyldimethyldecylammonium chloride, benzyldimethyldodecylammonium bromide, benzyldimethyldodecylammonium chloride, benzyldimethylhexadecylammonium chloride, benzyldimethyl(2-hydroxyethyl)ammonium chloride, benzyldimethyltetradecylammonium chloride and benzethonium chloride.
5. The hyaluronic acid complex of claim 4 comprising sodium hyaluronate and benzalconium chloride in a molar ratio of from about 10:1 to 1:10.
6. The hyaluronic acid complex of claim 1 wherein said complex is soluble in a mixture of from about 50 to about 60 weight percent 1,4-dioxane with from about 50 to about 40 weight percent water.
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Cited By (361)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050147642A1 (en) * 2003-12-19 2005-07-07 Laredo Walter R. Tissue scaffolds for use in muscoloskeletal repairs
US20050273178A1 (en) * 2004-02-06 2005-12-08 Boyan Barbara D Load bearing biocompatible device
US7682540B2 (en) 2004-02-06 2010-03-23 Georgia Tech Research Corporation Method of making hydrogel implants
US8293890B2 (en) * 2004-04-30 2012-10-23 Advanced Cardiovascular Systems, Inc. Hyaluronic acid based copolymers
US9155543B2 (en) 2011-05-26 2015-10-13 Cartiva, Inc. Tapered joint implant and related tools
CN107106694A (en) * 2015-01-13 2017-08-29 西格亚有限公司 The method for being used to prepare the butyric acid ester of hyaluroni in water
US9907663B2 (en) 2015-03-31 2018-03-06 Cartiva, Inc. Hydrogel implants with porous materials and methods
US10350072B2 (en) 2012-05-24 2019-07-16 Cartiva, Inc. Tooling for creating tapered opening in tissue and related methods
US10610224B2 (en) 2016-12-21 2020-04-07 Ethicon Llc Lockout arrangements for surgical end effectors and replaceable tool assemblies
US10617412B2 (en) 2015-03-06 2020-04-14 Ethicon Llc System for detecting the mis-insertion of a staple cartridge into a surgical stapler
US10617417B2 (en) 2014-11-06 2020-04-14 Ethicon Llc Staple cartridge comprising a releasable adjunct material
US10624861B2 (en) 2010-09-30 2020-04-21 Ethicon Llc Tissue thickness compensator configured to redistribute compressive forces
US10631859B2 (en) 2017-06-27 2020-04-28 Ethicon Llc Articulation systems for surgical instruments
US10639036B2 (en) 2008-02-14 2020-05-05 Ethicon Llc Robotically-controlled motorized surgical cutting and fastening instrument
US10646220B2 (en) 2017-06-20 2020-05-12 Ethicon Llc Systems and methods for controlling displacement member velocity for a surgical instrument
US10653435B2 (en) 2006-01-31 2020-05-19 Ethicon Llc Motor-driven surgical cutting and fastening instrument with tactile position feedback
US10660640B2 (en) 2008-02-14 2020-05-26 Ethicon Llc Motorized surgical cutting and fastening instrument
US10667809B2 (en) 2016-12-21 2020-06-02 Ethicon Llc Staple cartridge and staple cartridge channel comprising windows defined therein
US10667808B2 (en) 2012-03-28 2020-06-02 Ethicon Llc Staple cartridge comprising an absorbable adjunct
US10675028B2 (en) 2006-01-31 2020-06-09 Ethicon Llc Powered surgical instruments with firing system lockout arrangements
US10682142B2 (en) 2008-02-14 2020-06-16 Ethicon Llc Surgical stapling apparatus including an articulation system
US10682134B2 (en) 2017-12-21 2020-06-16 Ethicon Llc Continuous use self-propelled stapling instrument
US10682138B2 (en) 2016-12-21 2020-06-16 Ethicon Llc Bilaterally asymmetric staple forming pocket pairs
US10687817B2 (en) 2004-07-28 2020-06-23 Ethicon Llc Stapling device comprising a firing member lockout
US10687813B2 (en) 2017-12-15 2020-06-23 Ethicon Llc Adapters with firing stroke sensing arrangements for use in connection with electromechanical surgical instruments
US10687809B2 (en) 2016-12-21 2020-06-23 Ethicon Llc Surgical staple cartridge with movable camming member configured to disengage firing member lockout features
US10687812B2 (en) 2012-06-28 2020-06-23 Ethicon Llc Surgical instrument system including replaceable end effectors
US10687806B2 (en) 2015-03-06 2020-06-23 Ethicon Llc Adaptive tissue compression techniques to adjust closure rates for multiple tissue types
US10695057B2 (en) 2017-06-28 2020-06-30 Ethicon Llc Surgical instrument lockout arrangement
US10695058B2 (en) 2014-12-18 2020-06-30 Ethicon Llc Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member
US10695062B2 (en) 2010-10-01 2020-06-30 Ethicon Llc Surgical instrument including a retractable firing member
US10702266B2 (en) 2013-04-16 2020-07-07 Ethicon Llc Surgical instrument system
US10702267B2 (en) 2007-03-15 2020-07-07 Ethicon Llc Surgical stapling instrument having a releasable buttress material
US10716614B2 (en) 2017-06-28 2020-07-21 Ethicon Llc Surgical shaft assemblies with slip ring assemblies with increased contact pressure
USD890784S1 (en) 2017-06-20 2020-07-21 Ethicon Llc Display panel with changeable graphical user interface
US10716565B2 (en) 2017-12-19 2020-07-21 Ethicon Llc Surgical instruments with dual articulation drivers
US10729509B2 (en) 2017-12-19 2020-08-04 Ethicon Llc Surgical instrument comprising closure and firing locking mechanism
US10736634B2 (en) 2011-05-27 2020-08-11 Ethicon Llc Robotically-driven surgical instrument including a drive system
US10736630B2 (en) 2014-10-13 2020-08-11 Ethicon Llc Staple cartridge
US10736628B2 (en) 2008-09-23 2020-08-11 Ethicon Llc Motor-driven surgical cutting instrument
US10736636B2 (en) 2014-12-10 2020-08-11 Ethicon Llc Articulatable surgical instrument system
US10743851B2 (en) 2008-02-14 2020-08-18 Ethicon Llc Interchangeable tools for surgical instruments
US10743874B2 (en) 2017-12-15 2020-08-18 Ethicon Llc Sealed adapters for use with electromechanical surgical instruments
US10743872B2 (en) 2017-09-29 2020-08-18 Ethicon Llc System and methods for controlling a display of a surgical instrument
US10743870B2 (en) 2008-02-14 2020-08-18 Ethicon Llc Surgical stapling apparatus with interlockable firing system
US10743877B2 (en) 2010-09-30 2020-08-18 Ethicon Llc Surgical stapler with floating anvil
US10743873B2 (en) 2014-12-18 2020-08-18 Ethicon Llc Drive arrangements for articulatable surgical instruments
US10743849B2 (en) 2006-01-31 2020-08-18 Ethicon Llc Stapling system including an articulation system
US10743875B2 (en) 2017-12-15 2020-08-18 Ethicon Llc Surgical end effectors with jaw stiffener arrangements configured to permit monitoring of firing member
US10751076B2 (en) 2009-12-24 2020-08-25 Ethicon Llc Motor-driven surgical cutting instrument with electric actuator directional control assembly
US10758229B2 (en) 2016-12-21 2020-09-01 Ethicon Llc Surgical instrument comprising improved jaw control
US10758230B2 (en) 2016-12-21 2020-09-01 Ethicon Llc Surgical instrument with primary and safety processors
US10758374B2 (en) 2015-03-31 2020-09-01 Cartiva, Inc. Carpometacarpal (CMC) implants and methods
US10765427B2 (en) 2017-06-28 2020-09-08 Ethicon Llc Method for articulating a surgical instrument
US10765432B2 (en) 2008-02-14 2020-09-08 Ethicon Llc Surgical device including a control system
US10765429B2 (en) 2017-09-29 2020-09-08 Ethicon Llc Systems and methods for providing alerts according to the operational state of a surgical instrument
US10772625B2 (en) 2015-03-06 2020-09-15 Ethicon Llc Signal and power communication system positioned on a rotatable shaft
US10779821B2 (en) 2018-08-20 2020-09-22 Ethicon Llc Surgical stapler anvils with tissue stop features configured to avoid tissue pinch
US10779820B2 (en) 2017-06-20 2020-09-22 Ethicon Llc Systems and methods for controlling motor speed according to user input for a surgical instrument
US10780539B2 (en) 2011-05-27 2020-09-22 Ethicon Llc Stapling instrument for use with a robotic system
US10779824B2 (en) 2017-06-28 2020-09-22 Ethicon Llc Surgical instrument comprising an articulation system lockable by a closure system
US10779826B2 (en) 2017-12-15 2020-09-22 Ethicon Llc Methods of operating surgical end effectors
US10779903B2 (en) 2017-10-31 2020-09-22 Ethicon Llc Positive shaft rotation lock activated by jaw closure
US10779825B2 (en) 2017-12-15 2020-09-22 Ethicon Llc Adapters with end effector position sensing and control arrangements for use in connection with electromechanical surgical instruments
US10779823B2 (en) 2016-12-21 2020-09-22 Ethicon Llc Firing member pin angle
US10806449B2 (en) 2005-11-09 2020-10-20 Ethicon Llc End effectors for surgical staplers
US10806448B2 (en) 2014-12-18 2020-10-20 Ethicon Llc Surgical instrument assembly comprising a flexible articulation system
US10806450B2 (en) 2008-02-14 2020-10-20 Ethicon Llc Surgical cutting and fastening instrument having a control system
US10828032B2 (en) 2013-08-23 2020-11-10 Ethicon Llc End effector detection systems for surgical instruments
US10828033B2 (en) 2017-12-15 2020-11-10 Ethicon Llc Handheld electromechanical surgical instruments with improved motor control arrangements for positioning components of an adapter coupled thereto
US10835251B2 (en) 2010-09-30 2020-11-17 Ethicon Llc Surgical instrument assembly including an end effector configurable in different positions
US10835330B2 (en) 2017-12-19 2020-11-17 Ethicon Llc Method for determining the position of a rotatable jaw of a surgical instrument attachment assembly
US10842490B2 (en) 2017-10-31 2020-11-24 Ethicon Llc Cartridge body design with force reduction based on firing completion
US10842492B2 (en) 2018-08-20 2020-11-24 Ethicon Llc Powered articulatable surgical instruments with clutching and locking arrangements for linking an articulation drive system to a firing drive system
US10856869B2 (en) 2017-06-27 2020-12-08 Ethicon Llc Surgical anvil arrangements
US10856870B2 (en) 2018-08-20 2020-12-08 Ethicon Llc Switching arrangements for motor powered articulatable surgical instruments
US10863981B2 (en) 2014-03-26 2020-12-15 Ethicon Llc Interface systems for use with surgical instruments
US10863986B2 (en) 2015-09-23 2020-12-15 Ethicon Llc Surgical stapler having downstream current-based motor control
US10869666B2 (en) 2017-12-15 2020-12-22 Ethicon Llc Adapters with control systems for controlling multiple motors of an electromechanical surgical instrument
USD906355S1 (en) 2017-06-28 2020-12-29 Ethicon Llc Display screen or portion thereof with a graphical user interface for a surgical instrument
US10881399B2 (en) 2017-06-20 2021-01-05 Ethicon Llc Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument
USD907648S1 (en) 2017-09-29 2021-01-12 Ethicon Llc Display screen or portion thereof with animated graphical user interface
US10888321B2 (en) 2017-06-20 2021-01-12 Ethicon Llc Systems and methods for controlling velocity of a displacement member of a surgical stapling and cutting instrument
USD907647S1 (en) 2017-09-29 2021-01-12 Ethicon Llc Display screen or portion thereof with animated graphical user interface
US10893864B2 (en) 2016-12-21 2021-01-19 Ethicon Staple cartridges and arrangements of staples and staple cavities therein
US10893867B2 (en) 2013-03-14 2021-01-19 Ethicon Llc Drive train control arrangements for modular surgical instruments
US10903685B2 (en) 2017-06-28 2021-01-26 Ethicon Llc Surgical shaft assemblies with slip ring assemblies forming capacitive channels
US10898183B2 (en) 2017-06-29 2021-01-26 Ethicon Llc Robotic surgical instrument with closed loop feedback techniques for advancement of closure member during firing
US10905422B2 (en) 2016-12-21 2021-02-02 Ethicon Llc Surgical instrument for use with a robotic surgical system
US10905423B2 (en) 2014-09-05 2021-02-02 Ethicon Llc Smart cartridge wake up operation and data retention
US10905418B2 (en) 2014-10-16 2021-02-02 Ethicon Llc Staple cartridge comprising a tissue thickness compensator
US10912559B2 (en) 2018-08-20 2021-02-09 Ethicon Llc Reinforced deformable anvil tip for surgical stapler anvil
US10918386B2 (en) 2007-01-10 2021-02-16 Ethicon Llc Interlock and surgical instrument including same
USD910847S1 (en) 2017-12-19 2021-02-16 Ethicon Llc Surgical instrument assembly
US10932774B2 (en) 2005-08-31 2021-03-02 Ethicon Llc Surgical end effector for forming staples to different heights
US10932778B2 (en) 2008-10-10 2021-03-02 Ethicon Llc Powered surgical cutting and stapling apparatus with manually retractable firing system
US10932775B2 (en) 2012-06-28 2021-03-02 Ethicon Llc Firing system lockout arrangements for surgical instruments
US10932772B2 (en) 2017-06-29 2021-03-02 Ethicon Llc Methods for closed loop velocity control for robotic surgical instrument
US10932779B2 (en) 2015-09-30 2021-03-02 Ethicon Llc Compressible adjunct with crossing spacer fibers
US10945728B2 (en) 2014-12-18 2021-03-16 Ethicon Llc Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors
US10945731B2 (en) 2010-09-30 2021-03-16 Ethicon Llc Tissue thickness compensator comprising controlled release and expansion
USD914878S1 (en) 2018-08-20 2021-03-30 Ethicon Llc Surgical instrument anvil
US10959725B2 (en) 2012-06-15 2021-03-30 Ethicon Llc Articulatable surgical instrument comprising a firing drive
US10966718B2 (en) 2017-12-15 2021-04-06 Ethicon Llc Dynamic clamping assemblies with improved wear characteristics for use in connection with electromechanical surgical instruments
US10966627B2 (en) 2015-03-06 2021-04-06 Ethicon Llc Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures
US10980537B2 (en) 2017-06-20 2021-04-20 Ethicon Llc Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified number of shaft rotations
US10980535B2 (en) 2008-09-23 2021-04-20 Ethicon Llc Motorized surgical instrument with an end effector
US10980539B2 (en) 2015-09-30 2021-04-20 Ethicon Llc Implantable adjunct comprising bonded layers
US10987102B2 (en) 2010-09-30 2021-04-27 Ethicon Llc Tissue thickness compensator comprising a plurality of layers
USD917500S1 (en) 2017-09-29 2021-04-27 Ethicon Llc Display screen or portion thereof with graphical user interface
US10993717B2 (en) 2006-01-31 2021-05-04 Ethicon Llc Surgical stapling system comprising a control system
US10993716B2 (en) 2017-06-27 2021-05-04 Ethicon Llc Surgical anvil arrangements
US11000275B2 (en) 2006-01-31 2021-05-11 Ethicon Llc Surgical instrument
US11006951B2 (en) 2007-01-10 2021-05-18 Ethicon Llc Surgical instrument with wireless communication between control unit and sensor transponders
US11006955B2 (en) 2017-12-15 2021-05-18 Ethicon Llc End effectors with positive jaw opening features for use with adapters for electromechanical surgical instruments
US11007022B2 (en) 2017-06-29 2021-05-18 Ethicon Llc Closed loop velocity control techniques based on sensed tissue parameters for robotic surgical instrument
US11013511B2 (en) 2007-06-22 2021-05-25 Ethicon Llc Surgical stapling instrument with an articulatable end effector
US11020115B2 (en) 2014-02-12 2021-06-01 Cilag Gmbh International Deliverable surgical instrument
US11020112B2 (en) 2017-12-19 2021-06-01 Ethicon Llc Surgical tools configured for interchangeable use with different controller interfaces
US11026678B2 (en) 2015-09-23 2021-06-08 Cilag Gmbh International Surgical stapler having motor control based on an electrical parameter related to a motor current
US11026684B2 (en) 2016-04-15 2021-06-08 Ethicon Llc Surgical instrument with multiple program responses during a firing motion
US11033267B2 (en) 2017-12-15 2021-06-15 Ethicon Llc Systems and methods of controlling a clamping member firing rate of a surgical instrument
US11039834B2 (en) 2018-08-20 2021-06-22 Cilag Gmbh International Surgical stapler anvils with staple directing protrusions and tissue stability features
US11039836B2 (en) 2007-01-11 2021-06-22 Cilag Gmbh International Staple cartridge for use with a surgical stapling instrument
US11045192B2 (en) 2018-08-20 2021-06-29 Cilag Gmbh International Fabricating techniques for surgical stapler anvils
US11045270B2 (en) 2017-12-19 2021-06-29 Cilag Gmbh International Robotic attachment comprising exterior drive actuator
US11051807B2 (en) 2019-06-28 2021-07-06 Cilag Gmbh International Packaging assembly including a particulate trap
US11051813B2 (en) 2006-01-31 2021-07-06 Cilag Gmbh International Powered surgical instruments with firing system lockout arrangements
US11051810B2 (en) 2016-04-15 2021-07-06 Cilag Gmbh International Modular surgical instrument with configurable operating mode
US11058422B2 (en) 2015-12-30 2021-07-13 Cilag Gmbh International Mechanisms for compensating for battery pack failure in powered surgical instruments
US11058425B2 (en) 2015-08-17 2021-07-13 Ethicon Llc Implantable layers for a surgical instrument
US11071545B2 (en) 2014-09-05 2021-07-27 Cilag Gmbh International Smart cartridge wake up operation and data retention
US11071543B2 (en) 2017-12-15 2021-07-27 Cilag Gmbh International Surgical end effectors with clamping assemblies configured to increase jaw aperture ranges
US11071554B2 (en) 2017-06-20 2021-07-27 Cilag Gmbh International Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on magnitude of velocity error measurements
US11076929B2 (en) 2015-09-25 2021-08-03 Cilag Gmbh International Implantable adjunct systems for determining adjunct skew
US11076853B2 (en) 2017-12-21 2021-08-03 Cilag Gmbh International Systems and methods of displaying a knife position during transection for a surgical instrument
US11083453B2 (en) 2014-12-18 2021-08-10 Cilag Gmbh International Surgical stapling system including a flexible firing actuator and lateral buckling supports
US11083458B2 (en) 2018-08-20 2021-08-10 Cilag Gmbh International Powered surgical instruments with clutching arrangements to convert linear drive motions to rotary drive motions
US11083452B2 (en) 2010-09-30 2021-08-10 Cilag Gmbh International Staple cartridge including a tissue thickness compensator
US11083454B2 (en) 2015-12-30 2021-08-10 Cilag Gmbh International Mechanisms for compensating for drivetrain failure in powered surgical instruments
US11090046B2 (en) 2017-06-20 2021-08-17 Cilag Gmbh International Systems and methods for controlling displacement member motion of a surgical stapling and cutting instrument
US11090045B2 (en) 2005-08-31 2021-08-17 Cilag Gmbh International Staple cartridges for forming staples having differing formed staple heights
US11090075B2 (en) 2017-10-30 2021-08-17 Cilag Gmbh International Articulation features for surgical end effector
US11096689B2 (en) 2016-12-21 2021-08-24 Cilag Gmbh International Shaft assembly comprising a lockout
US11109859B2 (en) 2015-03-06 2021-09-07 Cilag Gmbh International Surgical instrument comprising a lockable battery housing
US11129613B2 (en) 2015-12-30 2021-09-28 Cilag Gmbh International Surgical instruments with separable motors and motor control circuits
US11129616B2 (en) 2011-05-27 2021-09-28 Cilag Gmbh International Surgical stapling system
US11133106B2 (en) 2013-08-23 2021-09-28 Cilag Gmbh International Surgical instrument assembly comprising a retraction assembly
US11129680B2 (en) 2017-12-21 2021-09-28 Cilag Gmbh International Surgical instrument comprising a projector
US11129615B2 (en) 2009-02-05 2021-09-28 Cilag Gmbh International Surgical stapling system
US11134944B2 (en) 2017-10-30 2021-10-05 Cilag Gmbh International Surgical stapler knife motion controls
US11134938B2 (en) 2007-06-04 2021-10-05 Cilag Gmbh International Robotically-controlled shaft based rotary drive systems for surgical instruments
US11135352B2 (en) 2004-07-28 2021-10-05 Cilag Gmbh International End effector including a gradually releasable medical adjunct
US11134942B2 (en) 2016-12-21 2021-10-05 Cilag Gmbh International Surgical stapling instruments and staple-forming anvils
US11134947B2 (en) 2005-08-31 2021-10-05 Cilag Gmbh International Fastener cartridge assembly comprising a camming sled with variable cam arrangements
US11141153B2 (en) 2014-10-29 2021-10-12 Cilag Gmbh International Staple cartridges comprising driver arrangements
US11147554B2 (en) 2016-04-18 2021-10-19 Cilag Gmbh International Surgical instrument system comprising a magnetic lockout
US11147553B2 (en) 2019-03-25 2021-10-19 Cilag Gmbh International Firing drive arrangements for surgical systems
US11147551B2 (en) 2019-03-25 2021-10-19 Cilag Gmbh International Firing drive arrangements for surgical systems
US11154297B2 (en) 2008-02-15 2021-10-26 Cilag Gmbh International Layer arrangements for surgical staple cartridges
US11154296B2 (en) 2010-09-30 2021-10-26 Cilag Gmbh International Anvil layer attached to a proximal end of an end effector
US11154301B2 (en) 2015-02-27 2021-10-26 Cilag Gmbh International Modular stapling assembly
US11172929B2 (en) 2019-03-25 2021-11-16 Cilag Gmbh International Articulation drive arrangements for surgical systems
US11179155B2 (en) 2016-12-21 2021-11-23 Cilag Gmbh International Anvil arrangements for surgical staplers
US11179150B2 (en) 2016-04-15 2021-11-23 Cilag Gmbh International Systems and methods for controlling a surgical stapling and cutting instrument
US11191545B2 (en) 2016-04-15 2021-12-07 Cilag Gmbh International Staple formation detection mechanisms
US11197670B2 (en) 2017-12-15 2021-12-14 Cilag Gmbh International Surgical end effectors with pivotal jaws configured to touch at their respective distal ends when fully closed
US11197671B2 (en) 2012-06-28 2021-12-14 Cilag Gmbh International Stapling assembly comprising a lockout
US11202633B2 (en) 2014-09-26 2021-12-21 Cilag Gmbh International Surgical stapling buttresses and adjunct materials
US11207065B2 (en) 2018-08-20 2021-12-28 Cilag Gmbh International Method for fabricating surgical stapler anvils
US11207064B2 (en) 2011-05-27 2021-12-28 Cilag Gmbh International Automated end effector component reloading system for use with a robotic system
US11213293B2 (en) 2016-02-09 2022-01-04 Cilag Gmbh International Articulatable surgical instruments with single articulation link arrangements
US11213302B2 (en) 2017-06-20 2022-01-04 Cilag Gmbh International Method for closed loop control of motor velocity of a surgical stapling and cutting instrument
US11219455B2 (en) 2019-06-28 2022-01-11 Cilag Gmbh International Surgical instrument including a lockout key
US11224428B2 (en) 2016-12-21 2022-01-18 Cilag Gmbh International Surgical stapling systems
US11224426B2 (en) 2016-02-12 2022-01-18 Cilag Gmbh International Mechanisms for compensating for drivetrain failure in powered surgical instruments
US11224427B2 (en) 2006-01-31 2022-01-18 Cilag Gmbh International Surgical stapling system including a console and retraction assembly
US11224423B2 (en) 2015-03-06 2022-01-18 Cilag Gmbh International Smart sensors with local signal processing
US11224497B2 (en) 2019-06-28 2022-01-18 Cilag Gmbh International Surgical systems with multiple RFID tags
US11229437B2 (en) 2019-06-28 2022-01-25 Cilag Gmbh International Method for authenticating the compatibility of a staple cartridge with a surgical instrument
US11234698B2 (en) 2019-12-19 2022-02-01 Cilag Gmbh International Stapling system comprising a clamp lockout and a firing lockout
US11241230B2 (en) 2012-06-28 2022-02-08 Cilag Gmbh International Clip applier tool for use with a robotic surgical system
US11246590B2 (en) 2005-08-31 2022-02-15 Cilag Gmbh International Staple cartridge including staple drivers having different unfired heights
US11246618B2 (en) 2013-03-01 2022-02-15 Cilag Gmbh International Surgical instrument soft stop
US11246678B2 (en) 2019-06-28 2022-02-15 Cilag Gmbh International Surgical stapling system having a frangible RFID tag
US11246592B2 (en) 2017-06-28 2022-02-15 Cilag Gmbh International Surgical instrument comprising an articulation system lockable to a frame
US11253254B2 (en) 2019-04-30 2022-02-22 Cilag Gmbh International Shaft rotation actuator on a surgical instrument
US11253256B2 (en) 2018-08-20 2022-02-22 Cilag Gmbh International Articulatable motor powered surgical instruments with dedicated articulation motor arrangements
US11259805B2 (en) 2017-06-28 2022-03-01 Cilag Gmbh International Surgical instrument comprising firing member supports
US11259803B2 (en) 2019-06-28 2022-03-01 Cilag Gmbh International Surgical stapling system having an information encryption protocol
US11259799B2 (en) 2014-03-26 2022-03-01 Cilag Gmbh International Interface systems for use with surgical instruments
US11266405B2 (en) 2017-06-27 2022-03-08 Cilag Gmbh International Surgical anvil manufacturing methods
US11266409B2 (en) 2014-04-16 2022-03-08 Cilag Gmbh International Fastener cartridge comprising a sled including longitudinally-staggered ramps
US11266406B2 (en) 2013-03-14 2022-03-08 Cilag Gmbh International Control systems for surgical instruments
US11272938B2 (en) 2006-06-27 2022-03-15 Cilag Gmbh International Surgical instrument including dedicated firing and retraction assemblies
US11278279B2 (en) 2006-01-31 2022-03-22 Cilag Gmbh International Surgical instrument assembly
US11284898B2 (en) 2014-09-18 2022-03-29 Cilag Gmbh International Surgical instrument including a deployable knife
US11291441B2 (en) 2007-01-10 2022-04-05 Cilag Gmbh International Surgical instrument with wireless communication between control unit and remote sensor
US11291447B2 (en) 2019-12-19 2022-04-05 Cilag Gmbh International Stapling instrument comprising independent jaw closing and staple firing systems
US11291451B2 (en) 2019-06-28 2022-04-05 Cilag Gmbh International Surgical instrument with battery compatibility verification functionality
US11291440B2 (en) 2018-08-20 2022-04-05 Cilag Gmbh International Method for operating a powered articulatable surgical instrument
US11291449B2 (en) 2009-12-24 2022-04-05 Cilag Gmbh International Surgical cutting instrument that analyzes tissue thickness
US11298132B2 (en) 2019-06-28 2022-04-12 Cilag GmbH Inlernational Staple cartridge including a honeycomb extension
US11298125B2 (en) 2010-09-30 2022-04-12 Cilag Gmbh International Tissue stapler having a thickness compensator
US11298127B2 (en) 2019-06-28 2022-04-12 Cilag GmbH Interational Surgical stapling system having a lockout mechanism for an incompatible cartridge
US11304696B2 (en) 2019-12-19 2022-04-19 Cilag Gmbh International Surgical instrument comprising a powered articulation system
US11304695B2 (en) 2017-08-03 2022-04-19 Cilag Gmbh International Surgical system shaft interconnection
US11311290B2 (en) 2017-12-21 2022-04-26 Cilag Gmbh International Surgical instrument comprising an end effector dampener
US11311294B2 (en) 2014-09-05 2022-04-26 Cilag Gmbh International Powered medical device including measurement of closure state of jaws
US11311292B2 (en) 2016-04-15 2022-04-26 Cilag Gmbh International Surgical instrument with detection sensors
US11317917B2 (en) 2016-04-18 2022-05-03 Cilag Gmbh International Surgical stapling system comprising a lockable firing assembly
US11317913B2 (en) 2016-12-21 2022-05-03 Cilag Gmbh International Lockout arrangements for surgical end effectors and replaceable tool assemblies
US11324501B2 (en) 2018-08-20 2022-05-10 Cilag Gmbh International Surgical stapling devices with improved closure members
US11324503B2 (en) 2017-06-27 2022-05-10 Cilag Gmbh International Surgical firing member arrangements
US11344303B2 (en) 2016-02-12 2022-05-31 Cilag Gmbh International Mechanisms for compensating for drivetrain failure in powered surgical instruments
US11350935B2 (en) 2016-12-21 2022-06-07 Cilag Gmbh International Surgical tool assemblies with closure stroke reduction features
US11350928B2 (en) 2016-04-18 2022-06-07 Cilag Gmbh International Surgical instrument comprising a tissue thickness lockout and speed control system
US11350932B2 (en) 2016-04-15 2022-06-07 Cilag Gmbh International Surgical instrument with improved stop/start control during a firing motion
US11376098B2 (en) 2019-06-28 2022-07-05 Cilag Gmbh International Surgical instrument system comprising an RFID system
US11382638B2 (en) 2017-06-20 2022-07-12 Cilag Gmbh International Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified displacement distance
US11382627B2 (en) 2014-04-16 2022-07-12 Cilag Gmbh International Surgical stapling assembly comprising a firing member including a lateral extension
US11399837B2 (en) 2019-06-28 2022-08-02 Cilag Gmbh International Mechanisms for motor control adjustments of a motorized surgical instrument
US11399829B2 (en) 2017-09-29 2022-08-02 Cilag Gmbh International Systems and methods of initiating a power shutdown mode for a surgical instrument
US11406380B2 (en) 2008-09-23 2022-08-09 Cilag Gmbh International Motorized surgical instrument
US11419606B2 (en) 2016-12-21 2022-08-23 Cilag Gmbh International Shaft assembly comprising a clutch configured to adapt the output of a rotary firing member to two different systems
US11426167B2 (en) 2019-06-28 2022-08-30 Cilag Gmbh International Mechanisms for proper anvil attachment surgical stapling head assembly
US11426251B2 (en) 2019-04-30 2022-08-30 Cilag Gmbh International Articulation directional lights on a surgical instrument
US11432816B2 (en) 2019-04-30 2022-09-06 Cilag Gmbh International Articulation pin for a surgical instrument
US11439470B2 (en) 2011-05-27 2022-09-13 Cilag Gmbh International Robotically-controlled surgical instrument with selectively articulatable end effector
US11446029B2 (en) 2019-12-19 2022-09-20 Cilag Gmbh International Staple cartridge comprising projections extending from a curved deck surface
US11452526B2 (en) 2020-10-29 2022-09-27 Cilag Gmbh International Surgical instrument comprising a staged voltage regulation start-up system
US11452528B2 (en) 2019-04-30 2022-09-27 Cilag Gmbh International Articulation actuators for a surgical instrument
US11457918B2 (en) 2014-10-29 2022-10-04 Cilag Gmbh International Cartridge assemblies for surgical staplers
US11464512B2 (en) 2019-12-19 2022-10-11 Cilag Gmbh International Staple cartridge comprising a curved deck surface
US11464513B2 (en) 2012-06-28 2022-10-11 Cilag Gmbh International Surgical instrument system including replaceable end effectors
USD966512S1 (en) 2020-06-02 2022-10-11 Cilag Gmbh International Staple cartridge
US11464601B2 (en) 2019-06-28 2022-10-11 Cilag Gmbh International Surgical instrument comprising an RFID system for tracking a movable component
US11471157B2 (en) 2019-04-30 2022-10-18 Cilag Gmbh International Articulation control mapping for a surgical instrument
USD967421S1 (en) 2020-06-02 2022-10-18 Cilag Gmbh International Staple cartridge
US11471155B2 (en) 2017-08-03 2022-10-18 Cilag Gmbh International Surgical system bailout
US11478241B2 (en) 2019-06-28 2022-10-25 Cilag Gmbh International Staple cartridge including projections
US11478247B2 (en) 2010-07-30 2022-10-25 Cilag Gmbh International Tissue acquisition arrangements and methods for surgical stapling devices
US11484311B2 (en) 2005-08-31 2022-11-01 Cilag Gmbh International Staple cartridge comprising a staple driver arrangement
US11484312B2 (en) 2005-08-31 2022-11-01 Cilag Gmbh International Staple cartridge comprising a staple driver arrangement
US11497488B2 (en) 2014-03-26 2022-11-15 Cilag Gmbh International Systems and methods for controlling a segmented circuit
US11497492B2 (en) 2019-06-28 2022-11-15 Cilag Gmbh International Surgical instrument including an articulation lock
US11504116B2 (en) 2011-04-29 2022-11-22 Cilag Gmbh International Layer of material for a surgical end effector
US11504122B2 (en) 2019-12-19 2022-11-22 Cilag Gmbh International Surgical instrument comprising a nested firing member
US11517325B2 (en) 2017-06-20 2022-12-06 Cilag Gmbh International Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured displacement distance traveled over a specified time interval
US11517315B2 (en) 2014-04-16 2022-12-06 Cilag Gmbh International Fastener cartridges including extensions having different configurations
US11517390B2 (en) 2020-10-29 2022-12-06 Cilag Gmbh International Surgical instrument comprising a limited travel switch
US11523822B2 (en) 2019-06-28 2022-12-13 Cilag Gmbh International Battery pack including a circuit interrupter
US11523823B2 (en) 2016-02-09 2022-12-13 Cilag Gmbh International Surgical instruments with non-symmetrical articulation arrangements
US11523821B2 (en) 2014-09-26 2022-12-13 Cilag Gmbh International Method for creating a flexible staple line
US11529137B2 (en) 2019-12-19 2022-12-20 Cilag Gmbh International Staple cartridge comprising driver retention members
US11529138B2 (en) 2013-03-01 2022-12-20 Cilag Gmbh International Powered surgical instrument including a rotary drive screw
US11529139B2 (en) 2019-12-19 2022-12-20 Cilag Gmbh International Motor driven surgical instrument
US11534259B2 (en) 2020-10-29 2022-12-27 Cilag Gmbh International Surgical instrument comprising an articulation indicator
USD974560S1 (en) 2020-06-02 2023-01-03 Cilag Gmbh International Staple cartridge
USD975278S1 (en) 2020-06-02 2023-01-10 Cilag Gmbh International Staple cartridge
USD975850S1 (en) 2020-06-02 2023-01-17 Cilag Gmbh International Staple cartridge
US11553971B2 (en) 2019-06-28 2023-01-17 Cilag Gmbh International Surgical RFID assemblies for display and communication
USD975851S1 (en) 2020-06-02 2023-01-17 Cilag Gmbh International Staple cartridge
US11559304B2 (en) 2019-12-19 2023-01-24 Cilag Gmbh International Surgical instrument comprising a rapid closure mechanism
USD976401S1 (en) 2020-06-02 2023-01-24 Cilag Gmbh International Staple cartridge
US11564682B2 (en) 2007-06-04 2023-01-31 Cilag Gmbh International Surgical stapler device
US11564686B2 (en) 2017-06-28 2023-01-31 Cilag Gmbh International Surgical shaft assemblies with flexible interfaces
US11571215B2 (en) 2010-09-30 2023-02-07 Cilag Gmbh International Layer of material for a surgical end effector
US11571231B2 (en) 2006-09-29 2023-02-07 Cilag Gmbh International Staple cartridge having a driver for driving multiple staples
US11576672B2 (en) 2019-12-19 2023-02-14 Cilag Gmbh International Surgical instrument comprising a closure system including a closure member and an opening member driven by a drive screw
USD980425S1 (en) 2020-10-29 2023-03-07 Cilag Gmbh International Surgical instrument assembly
US11607239B2 (en) 2016-04-15 2023-03-21 Cilag Gmbh International Systems and methods for controlling a surgical stapling and cutting instrument
US11607219B2 (en) 2019-12-19 2023-03-21 Cilag Gmbh International Staple cartridge comprising a detachable tissue cutting knife
US11612393B2 (en) 2006-01-31 2023-03-28 Cilag Gmbh International Robotically-controlled end effector
US11617577B2 (en) 2020-10-29 2023-04-04 Cilag Gmbh International Surgical instrument comprising a sensor configured to sense whether an articulation drive of the surgical instrument is actuatable
US11622763B2 (en) 2013-04-16 2023-04-11 Cilag Gmbh International Stapling assembly comprising a shiftable drive
US11622766B2 (en) 2012-06-28 2023-04-11 Cilag Gmbh International Empty clip cartridge lockout
US11627959B2 (en) 2019-06-28 2023-04-18 Cilag Gmbh International Surgical instruments including manual and powered system lockouts
US11627960B2 (en) 2020-12-02 2023-04-18 Cilag Gmbh International Powered surgical instruments with smart reload with separately attachable exteriorly mounted wiring connections
US11638587B2 (en) 2019-06-28 2023-05-02 Cilag Gmbh International RFID identification systems for surgical instruments
US11638582B2 (en) 2020-07-28 2023-05-02 Cilag Gmbh International Surgical instruments with torsion spine drive arrangements
US11642125B2 (en) 2016-04-15 2023-05-09 Cilag Gmbh International Robotic surgical system including a user interface and a control circuit
US11648005B2 (en) 2008-09-23 2023-05-16 Cilag Gmbh International Robotically-controlled motorized surgical instrument with an end effector
US11648009B2 (en) 2019-04-30 2023-05-16 Cilag Gmbh International Rotatable jaw tip for a surgical instrument
US11653915B2 (en) 2020-12-02 2023-05-23 Cilag Gmbh International Surgical instruments with sled location detection and adjustment features
US11653920B2 (en) 2020-12-02 2023-05-23 Cilag Gmbh International Powered surgical instruments with communication interfaces through sterile barrier
US11653914B2 (en) 2017-06-20 2023-05-23 Cilag Gmbh International Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument according to articulation angle of end effector
US11660163B2 (en) 2019-06-28 2023-05-30 Cilag Gmbh International Surgical system with RFID tags for updating motor assembly parameters
US11678882B2 (en) 2020-12-02 2023-06-20 Cilag Gmbh International Surgical instruments with interactive features to remedy incidental sled movements
US11678877B2 (en) 2014-12-18 2023-06-20 Cilag Gmbh International Surgical instrument including a flexible support configured to support a flexible firing member
US11684434B2 (en) 2019-06-28 2023-06-27 Cilag Gmbh International Surgical RFID assemblies for instrument operational setting control
US11690623B2 (en) 2015-09-30 2023-07-04 Cilag Gmbh International Method for applying an implantable layer to a fastener cartridge
US11696761B2 (en) 2019-03-25 2023-07-11 Cilag Gmbh International Firing drive arrangements for surgical systems
US11696757B2 (en) 2021-02-26 2023-07-11 Cilag Gmbh International Monitoring of internal systems to detect and track cartridge motion status
US11701111B2 (en) 2019-12-19 2023-07-18 Cilag Gmbh International Method for operating a surgical stapling instrument
US11701113B2 (en) 2021-02-26 2023-07-18 Cilag Gmbh International Stapling instrument comprising a separate power antenna and a data transfer antenna
US11717294B2 (en) 2014-04-16 2023-08-08 Cilag Gmbh International End effector arrangements comprising indicators
US11717289B2 (en) 2020-10-29 2023-08-08 Cilag Gmbh International Surgical instrument comprising an indicator which indicates that an articulation drive is actuatable
US11717291B2 (en) 2021-03-22 2023-08-08 Cilag Gmbh International Staple cartridge comprising staples configured to apply different tissue compression
US11723662B2 (en) 2021-05-28 2023-08-15 Cilag Gmbh International Stapling instrument comprising an articulation control display
US11723658B2 (en) 2021-03-22 2023-08-15 Cilag Gmbh International Staple cartridge comprising a firing lockout
US11723657B2 (en) 2021-02-26 2023-08-15 Cilag Gmbh International Adjustable communication based on available bandwidth and power capacity
US11730473B2 (en) 2021-02-26 2023-08-22 Cilag Gmbh International Monitoring of manufacturing life-cycle
US11737749B2 (en) 2021-03-22 2023-08-29 Cilag Gmbh International Surgical stapling instrument comprising a retraction system
US11737751B2 (en) 2020-12-02 2023-08-29 Cilag Gmbh International Devices and methods of managing energy dissipated within sterile barriers of surgical instrument housings
US11744603B2 (en) 2021-03-24 2023-09-05 Cilag Gmbh International Multi-axis pivot joints for surgical instruments and methods for manufacturing same
US11744581B2 (en) 2020-12-02 2023-09-05 Cilag Gmbh International Powered surgical instruments with multi-phase tissue treatment
US11744583B2 (en) 2021-02-26 2023-09-05 Cilag Gmbh International Distal communication array to tune frequency of RF systems
US11749877B2 (en) 2021-02-26 2023-09-05 Cilag Gmbh International Stapling instrument comprising a signal antenna
US11751869B2 (en) 2021-02-26 2023-09-12 Cilag Gmbh International Monitoring of multiple sensors over time to detect moving characteristics of tissue
US11759202B2 (en) 2021-03-22 2023-09-19 Cilag Gmbh International Staple cartridge comprising an implantable layer
US11766260B2 (en) 2016-12-21 2023-09-26 Cilag Gmbh International Methods of stapling tissue
US11766259B2 (en) 2016-12-21 2023-09-26 Cilag Gmbh International Method of deforming staples from two different types of staple cartridges with the same surgical stapling instrument
US11771419B2 (en) 2019-06-28 2023-10-03 Cilag Gmbh International Packaging for a replaceable component of a surgical stapling system
US11779420B2 (en) 2012-06-28 2023-10-10 Cilag Gmbh International Robotic surgical attachments having manually-actuated retraction assemblies
US11779330B2 (en) 2020-10-29 2023-10-10 Cilag Gmbh International Surgical instrument comprising a jaw alignment system
US11786243B2 (en) 2021-03-24 2023-10-17 Cilag Gmbh International Firing members having flexible portions for adapting to a load during a surgical firing stroke
US11786239B2 (en) 2021-03-24 2023-10-17 Cilag Gmbh International Surgical instrument articulation joint arrangements comprising multiple moving linkage features
US11793518B2 (en) 2006-01-31 2023-10-24 Cilag Gmbh International Powered surgical instruments with firing system lockout arrangements
US11793516B2 (en) 2021-03-24 2023-10-24 Cilag Gmbh International Surgical staple cartridge comprising longitudinal support beam
US11793514B2 (en) 2021-02-26 2023-10-24 Cilag Gmbh International Staple cartridge comprising sensor array which may be embedded in cartridge body
US11793522B2 (en) 2015-09-30 2023-10-24 Cilag Gmbh International Staple cartridge assembly including a compressible adjunct
US11806011B2 (en) 2021-03-22 2023-11-07 Cilag Gmbh International Stapling instrument comprising tissue compression systems
US11812964B2 (en) 2021-02-26 2023-11-14 Cilag Gmbh International Staple cartridge comprising a power management circuit
US11826012B2 (en) 2021-03-22 2023-11-28 Cilag Gmbh International Stapling instrument comprising a pulsed motor-driven firing rack
US11826048B2 (en) 2017-06-28 2023-11-28 Cilag Gmbh International Surgical instrument comprising selectively actuatable rotatable couplers
US11826042B2 (en) 2021-03-22 2023-11-28 Cilag Gmbh International Surgical instrument comprising a firing drive including a selectable leverage mechanism
US11826132B2 (en) 2015-03-06 2023-11-28 Cilag Gmbh International Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures
US11832816B2 (en) 2021-03-24 2023-12-05 Cilag Gmbh International Surgical stapling assembly comprising nonplanar staples and planar staples
US11839352B2 (en) 2007-01-11 2023-12-12 Cilag Gmbh International Surgical stapling device with an end effector
US11844518B2 (en) 2020-10-29 2023-12-19 Cilag Gmbh International Method for operating a surgical instrument
US11844520B2 (en) 2019-12-19 2023-12-19 Cilag Gmbh International Staple cartridge comprising driver retention members
US11849944B2 (en) 2021-03-24 2023-12-26 Cilag Gmbh International Drivers for fastener cartridge assemblies having rotary drive screws
US11849943B2 (en) 2020-12-02 2023-12-26 Cilag Gmbh International Surgical instrument with cartridge release mechanisms
US11849945B2 (en) 2021-03-24 2023-12-26 Cilag Gmbh International Rotary-driven surgical stapling assembly comprising eccentrically driven firing member
US11849941B2 (en) 2007-06-29 2023-12-26 Cilag Gmbh International Staple cartridge having staple cavities extending at a transverse angle relative to a longitudinal cartridge axis
US11849952B2 (en) 2010-09-30 2023-12-26 Cilag Gmbh International Staple cartridge comprising staples positioned within a compressible portion thereof
US11857183B2 (en) 2021-03-24 2024-01-02 Cilag Gmbh International Stapling assembly components having metal substrates and plastic bodies
US11877745B2 (en) 2021-10-18 2024-01-23 Cilag Gmbh International Surgical stapling assembly having longitudinally-repeating staple leg clusters
US11883020B2 (en) 2006-01-31 2024-01-30 Cilag Gmbh International Surgical instrument having a feedback system
USD1013170S1 (en) 2020-10-29 2024-01-30 Cilag Gmbh International Surgical instrument assembly
US11883026B2 (en) 2014-04-16 2024-01-30 Cilag Gmbh International Fastener cartridge assemblies and staple retainer cover arrangements
US11890012B2 (en) 2004-07-28 2024-02-06 Cilag Gmbh International Staple cartridge comprising cartridge body and attached support
US11890010B2 (en) 2020-12-02 2024-02-06 Cllag GmbH International Dual-sided reinforced reload for surgical instruments
US11896219B2 (en) 2021-03-24 2024-02-13 Cilag Gmbh International Mating features between drivers and underside of a cartridge deck
US11896218B2 (en) 2021-03-24 2024-02-13 Cilag Gmbh International Method of using a powered stapling device
US11896217B2 (en) 2020-10-29 2024-02-13 Cilag Gmbh International Surgical instrument comprising an articulation lock
US11903581B2 (en) 2019-04-30 2024-02-20 Cilag Gmbh International Methods for stapling tissue using a surgical instrument
US11903582B2 (en) 2021-03-24 2024-02-20 Cilag Gmbh International Leveraging surfaces for cartridge installation
US11911032B2 (en) 2019-12-19 2024-02-27 Cilag Gmbh International Staple cartridge comprising a seating cam
US11918220B2 (en) 2012-03-28 2024-03-05 Cilag Gmbh International Tissue thickness compensator comprising tissue ingrowth features
US11918212B2 (en) 2015-03-31 2024-03-05 Cilag Gmbh International Surgical instrument with selectively disengageable drive systems
US11925349B2 (en) 2021-02-26 2024-03-12 Cilag Gmbh International Adjustment to transfer parameters to improve available power
US11931025B2 (en) 2020-10-29 2024-03-19 Cilag Gmbh International Surgical instrument comprising a releasable closure drive lock
US11931033B2 (en) 2019-12-19 2024-03-19 Cilag Gmbh International Staple cartridge comprising a latch lockout
US11937816B2 (en) 2021-10-28 2024-03-26 Cilag Gmbh International Electrical lead arrangements for surgical instruments
US11944296B2 (en) 2020-12-02 2024-04-02 Cilag Gmbh International Powered surgical instruments with external connectors
US11944336B2 (en) 2021-03-24 2024-04-02 Cilag Gmbh International Joint arrangements for multi-planar alignment and support of operational drive shafts in articulatable surgical instruments
US11944300B2 (en) 2017-08-03 2024-04-02 Cilag Gmbh International Method for operating a surgical system bailout
US11944338B2 (en) 2015-03-06 2024-04-02 Cilag Gmbh International Multiple level thresholds to modify operation of powered surgical instruments
US11950779B2 (en) 2021-02-26 2024-04-09 Cilag Gmbh International Method of powering and communicating with a staple cartridge

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2404920A (en) * 2003-08-12 2005-02-16 Johnson & Johnson Medical Ltd Antimicrobial polymer
JP5178506B2 (en) * 2005-03-14 2013-04-10 バイオベンション ホールディングス リミテッド Methods related to drug delivery compositions
KR101122163B1 (en) * 2009-12-01 2012-03-16 (주)셀인바이오 Hyaluronic acid derivative with atopic dermatitis treating effect and method of preparing the same
CN105418803A (en) * 2015-12-30 2016-03-23 山东天晟生物科技有限公司 Esterification method for hyaluronic acid

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4713448A (en) 1985-03-12 1987-12-15 Biomatrix, Inc. Chemically modified hyaluronic acid preparation and method of recovery thereof from animal tissues
US4851521A (en) 1985-07-08 1989-07-25 Fidia, S.P.A. Esters of hyaluronic acid
US5017229A (en) 1990-06-25 1991-05-21 Genzyme Corporation Water insoluble derivatives of hyaluronic acid
US5356883A (en) 1989-08-01 1994-10-18 Research Foundation Of State University Of N.Y. Water-insoluble derivatives of hyaluronic acid and their methods of preparation and use
WO1995015168A1 (en) 1993-11-30 1995-06-08 The Research Foundation Of State University Of New York Functionalized derivatives of hyaluronic acid
US5658582A (en) 1993-02-12 1997-08-19 Fidia Advanced Biopolymers S.R.L. Multilayer nonwoven tissue containing a surface layer comprising at least one hyaluronic acid ester
WO1997045532A1 (en) 1996-05-28 1997-12-04 Brown University Research Foundation Hyaluronan based biodegradable scaffolds for tissue repair
US5735863A (en) 1991-02-11 1998-04-07 Fidia S.P.A. Biodegradable and bioabsorbable guide channels for use in nerve treatment and regeneration
US5925626A (en) 1983-10-10 1999-07-20 Fidia S.P.A. Hyaluronic acid fractions having pharmaceutical activity, and pharmaceutical compositions containing the same

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5925626A (en) 1983-10-10 1999-07-20 Fidia S.P.A. Hyaluronic acid fractions having pharmaceutical activity, and pharmaceutical compositions containing the same
US4713448A (en) 1985-03-12 1987-12-15 Biomatrix, Inc. Chemically modified hyaluronic acid preparation and method of recovery thereof from animal tissues
US4851521A (en) 1985-07-08 1989-07-25 Fidia, S.P.A. Esters of hyaluronic acid
US5336767A (en) 1985-07-08 1994-08-09 Fidia, S.P.A. Total or partial esters of hyaluronic acid
US5356883A (en) 1989-08-01 1994-10-18 Research Foundation Of State University Of N.Y. Water-insoluble derivatives of hyaluronic acid and their methods of preparation and use
US5017229A (en) 1990-06-25 1991-05-21 Genzyme Corporation Water insoluble derivatives of hyaluronic acid
US5735863A (en) 1991-02-11 1998-04-07 Fidia S.P.A. Biodegradable and bioabsorbable guide channels for use in nerve treatment and regeneration
US5658582A (en) 1993-02-12 1997-08-19 Fidia Advanced Biopolymers S.R.L. Multilayer nonwoven tissue containing a surface layer comprising at least one hyaluronic acid ester
WO1995015168A1 (en) 1993-11-30 1995-06-08 The Research Foundation Of State University Of New York Functionalized derivatives of hyaluronic acid
WO1997045532A1 (en) 1996-05-28 1997-12-04 Brown University Research Foundation Hyaluronan based biodegradable scaffolds for tissue repair

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
Birotto,D.; Urbani,S.; Bru, P., Prnier, D.; Barbucci, R. Abatangelo, G. "Tissue-specific gene expression in chondrocytes grown on three-dimensional hyaluronic acid scaffolds, "Biomateroals (203), 24, 3265-3275.
Bulpitt, P.; Aeschlimann D. "New strategy for chemical modification of hyaluronic acid; preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels," Journal of Biomedical Materials (1999), 47, 152-169.
Cascone, M.G.; Sim, B.; Downes, S. "Blends of synthetic and natural polymers as drug delivery systems for growth hormone," Biomaterails (1995), 16, 569-74.
Dausse, Y.; Grossin, L.; Miralles, G.; Peletier, S.; Mainard, D.; Hubert, P.; Baptise, D.; Glllet, P.; Dellacherie, E; Netter, P.; Payan, E. "Cartilage repair using new polysaccharidic biomaterials; macrosocpic, histological and biochemical approaches in a rat model of cartilage defect," Osteoarthritic and Cartilage (2003 Jan.), 11, 16-28.
Drury, J.L.; Mooney, D.J. "Hydrogels for tissue engineering; scaffold design variables and applications," Biomaterials (2003), 24, 4337-4351.
Halbleib, M.; Skurk, T.; de Luca, C.; von Heimburg, D.; Hauner, H. "Tissue engineering of white adipose tissue using hyaluronic acid-based scaffolds. I: Invitro differentiation of human adipocyte precursor cells on scaffolds," Biomaterials (2003), 24, 3125-3132.
Luo, Y.; Kirker, K.R.; Prestwich, G.D. "Cross-inked hyaluronic acid hydrogel films; new ibomaterials for drug delivery," Journal of Controlled Release (2000), 69, 169-184.
Miilella, E.; Brescia, E.; Massaro, C.; Ramires, P.,A.; Miglietta, M.R.; Fiori V.; Aversa, P. "Physico-chemical properties and degradability of non-woven hyaluronan benzylic esters as tissue engineering scaffolds", Biomaterials (2001), 23, 1053-1063.
Pianigiani, E.; Andreassi, A.; Taddeucci, P.; Allessandrini, C.; Fimiani, M. Andressi, L. "A new model for studying differentiation and growth of epidermal cultures on hyaluronan-based carrier," Biomaterials (1999), 20, 1689-1694.
Prestwich, G.D.; Marecak, D.M.; Marecek, J.F.; Vercuysse, K.P.; Ziebell, M.R. "Controlled chemical modification of hyaluronic acid: synthesis, appications and biodegradation of hydrazide derivatives", Journal of Controlled Release (1998), 53, 93-103.

Cited By (665)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7625581B2 (en) * 2003-12-19 2009-12-01 Ethicon, Inc. Tissue scaffolds for use in muscoloskeletal repairs
US20050147642A1 (en) * 2003-12-19 2005-07-07 Laredo Walter R. Tissue scaffolds for use in muscoloskeletal repairs
US8895073B2 (en) 2004-02-06 2014-11-25 Georgia Tech Research Corporation Hydrogel implant with superficial pores
US20050273178A1 (en) * 2004-02-06 2005-12-08 Boyan Barbara D Load bearing biocompatible device
US8002830B2 (en) 2004-02-06 2011-08-23 Georgia Tech Research Corporation Surface directed cellular attachment
US8142808B2 (en) 2004-02-06 2012-03-27 Georgia Tech Research Corporation Method of treating joints with hydrogel implants
US8318192B2 (en) 2004-02-06 2012-11-27 Georgia Tech Research Corporation Method of making load bearing hydrogel implants
US8486436B2 (en) 2004-02-06 2013-07-16 Georgia Tech Research Corporation Articular joint implant
US7910124B2 (en) 2004-02-06 2011-03-22 Georgia Tech Research Corporation Load bearing biocompatible device
US7682540B2 (en) 2004-02-06 2010-03-23 Georgia Tech Research Corporation Method of making hydrogel implants
US8906394B2 (en) 2004-04-30 2014-12-09 Advanced Cardiovascular Systems, Inc. Hyaluronic acid based copolymers
US8293890B2 (en) * 2004-04-30 2012-10-23 Advanced Cardiovascular Systems, Inc. Hyaluronic acid based copolymers
US8734817B2 (en) 2004-04-30 2014-05-27 Advanced Cardiovascular Systems, Inc. Hyaluronic acid based copolymers
US9101697B2 (en) 2004-04-30 2015-08-11 Abbott Cardiovascular Systems Inc. Hyaluronic acid based copolymers
US8846836B2 (en) 2004-04-30 2014-09-30 Advanced Cardiovascular Systems, Inc. Hyaluronic acid based copolymers
US11812960B2 (en) 2004-07-28 2023-11-14 Cilag Gmbh International Method of segmenting the operation of a surgical stapling instrument
US11890012B2 (en) 2004-07-28 2024-02-06 Cilag Gmbh International Staple cartridge comprising cartridge body and attached support
US11896225B2 (en) 2004-07-28 2024-02-13 Cilag Gmbh International Staple cartridge comprising a pan
US11882987B2 (en) 2004-07-28 2024-01-30 Cilag Gmbh International Articulating surgical stapling instrument incorporating a two-piece E-beam firing mechanism
US10716563B2 (en) 2004-07-28 2020-07-21 Ethicon Llc Stapling system comprising an instrument assembly including a lockout
US10687817B2 (en) 2004-07-28 2020-06-23 Ethicon Llc Stapling device comprising a firing member lockout
US11083456B2 (en) 2004-07-28 2021-08-10 Cilag Gmbh International Articulating surgical instrument incorporating a two-piece firing mechanism
US11116502B2 (en) 2004-07-28 2021-09-14 Cilag Gmbh International Surgical stapling instrument incorporating a two-piece firing mechanism
US11135352B2 (en) 2004-07-28 2021-10-05 Cilag Gmbh International End effector including a gradually releasable medical adjunct
US11684365B2 (en) 2004-07-28 2023-06-27 Cilag Gmbh International Replaceable staple cartridges for surgical instruments
US11576673B2 (en) 2005-08-31 2023-02-14 Cilag Gmbh International Stapling assembly for forming staples to different heights
US11246590B2 (en) 2005-08-31 2022-02-15 Cilag Gmbh International Staple cartridge including staple drivers having different unfired heights
US11134947B2 (en) 2005-08-31 2021-10-05 Cilag Gmbh International Fastener cartridge assembly comprising a camming sled with variable cam arrangements
US11172927B2 (en) 2005-08-31 2021-11-16 Cilag Gmbh International Staple cartridges for forming staples having differing formed staple heights
US11839375B2 (en) 2005-08-31 2023-12-12 Cilag Gmbh International Fastener cartridge assembly comprising an anvil and different staple heights
US11484312B2 (en) 2005-08-31 2022-11-01 Cilag Gmbh International Staple cartridge comprising a staple driver arrangement
US11793512B2 (en) 2005-08-31 2023-10-24 Cilag Gmbh International Staple cartridges for forming staples having differing formed staple heights
US11484311B2 (en) 2005-08-31 2022-11-01 Cilag Gmbh International Staple cartridge comprising a staple driver arrangement
US11399828B2 (en) 2005-08-31 2022-08-02 Cilag Gmbh International Fastener cartridge assembly comprising a fixed anvil and different staple heights
US11179153B2 (en) 2005-08-31 2021-11-23 Cilag Gmbh International Staple cartridges for forming staples having differing formed staple heights
US10932774B2 (en) 2005-08-31 2021-03-02 Ethicon Llc Surgical end effector for forming staples to different heights
US11771425B2 (en) 2005-08-31 2023-10-03 Cilag Gmbh International Stapling assembly for forming staples to different formed heights
US11090045B2 (en) 2005-08-31 2021-08-17 Cilag Gmbh International Staple cartridges for forming staples having differing formed staple heights
US11272928B2 (en) 2005-08-31 2022-03-15 Cilag GmbH Intemational Staple cartridges for forming staples having differing formed staple heights
US11730474B2 (en) 2005-08-31 2023-08-22 Cilag Gmbh International Fastener cartridge assembly comprising a movable cartridge and a staple driver arrangement
US10806449B2 (en) 2005-11-09 2020-10-20 Ethicon Llc End effectors for surgical staplers
US10993713B2 (en) 2005-11-09 2021-05-04 Ethicon Llc Surgical instruments
US11793511B2 (en) 2005-11-09 2023-10-24 Cilag Gmbh International Surgical instruments
US11801051B2 (en) 2006-01-31 2023-10-31 Cilag Gmbh International Accessing data stored in a memory of a surgical instrument
US11364046B2 (en) 2006-01-31 2022-06-21 Cilag Gmbh International Motor-driven surgical cutting and fastening instrument with tactile position feedback
US11890029B2 (en) 2006-01-31 2024-02-06 Cilag Gmbh International Motor-driven surgical cutting and fastening instrument
US11278279B2 (en) 2006-01-31 2022-03-22 Cilag Gmbh International Surgical instrument assembly
US11660110B2 (en) 2006-01-31 2023-05-30 Cilag Gmbh International Motor-driven surgical cutting and fastening instrument with tactile position feedback
US10709468B2 (en) 2006-01-31 2020-07-14 Ethicon Llc Motor-driven surgical cutting and fastening instrument
US11648008B2 (en) 2006-01-31 2023-05-16 Cilag Gmbh International Surgical instrument having force feedback capabilities
US11103269B2 (en) 2006-01-31 2021-08-31 Cilag Gmbh International Motor-driven surgical cutting and fastening instrument with tactile position feedback
US10893853B2 (en) 2006-01-31 2021-01-19 Ethicon Llc Stapling assembly including motor drive systems
US11883020B2 (en) 2006-01-31 2024-01-30 Cilag Gmbh International Surgical instrument having a feedback system
US11612393B2 (en) 2006-01-31 2023-03-28 Cilag Gmbh International Robotically-controlled end effector
US11350916B2 (en) 2006-01-31 2022-06-07 Cilag Gmbh International Endoscopic surgical instrument with a handle that can articulate with respect to the shaft
US10952728B2 (en) 2006-01-31 2021-03-23 Ethicon Llc Powered surgical instruments with firing system lockout arrangements
US10653435B2 (en) 2006-01-31 2020-05-19 Ethicon Llc Motor-driven surgical cutting and fastening instrument with tactile position feedback
US11224454B2 (en) 2006-01-31 2022-01-18 Cilag Gmbh International Motor-driven surgical cutting and fastening instrument with tactile position feedback
US11020113B2 (en) 2006-01-31 2021-06-01 Cilag Gmbh International Surgical instrument having force feedback capabilities
US11944299B2 (en) 2006-01-31 2024-04-02 Cilag Gmbh International Surgical instrument having force feedback capabilities
US10675028B2 (en) 2006-01-31 2020-06-09 Ethicon Llc Powered surgical instruments with firing system lockout arrangements
US11058420B2 (en) 2006-01-31 2021-07-13 Cilag Gmbh International Surgical stapling apparatus comprising a lockout system
US11890008B2 (en) 2006-01-31 2024-02-06 Cilag Gmbh International Surgical instrument with firing lockout
US11051813B2 (en) 2006-01-31 2021-07-06 Cilag Gmbh International Powered surgical instruments with firing system lockout arrangements
US10806479B2 (en) 2006-01-31 2020-10-20 Ethicon Llc Motor-driven surgical cutting and fastening instrument with tactile position feedback
US11166717B2 (en) 2006-01-31 2021-11-09 Cilag Gmbh International Surgical instrument with firing lockout
US10743849B2 (en) 2006-01-31 2020-08-18 Ethicon Llc Stapling system including an articulation system
US11793518B2 (en) 2006-01-31 2023-10-24 Cilag Gmbh International Powered surgical instruments with firing system lockout arrangements
US10993717B2 (en) 2006-01-31 2021-05-04 Ethicon Llc Surgical stapling system comprising a control system
US11224427B2 (en) 2006-01-31 2022-01-18 Cilag Gmbh International Surgical stapling system including a console and retraction assembly
US11246616B2 (en) 2006-01-31 2022-02-15 Cilag Gmbh International Motor-driven surgical cutting and fastening instrument with tactile position feedback
US11648024B2 (en) 2006-01-31 2023-05-16 Cilag Gmbh International Motor-driven surgical cutting and fastening instrument with position feedback
US11000275B2 (en) 2006-01-31 2021-05-11 Ethicon Llc Surgical instrument
US11272938B2 (en) 2006-06-27 2022-03-15 Cilag Gmbh International Surgical instrument including dedicated firing and retraction assemblies
US11571231B2 (en) 2006-09-29 2023-02-07 Cilag Gmbh International Staple cartridge having a driver for driving multiple staples
US11622785B2 (en) 2006-09-29 2023-04-11 Cilag Gmbh International Surgical staples having attached drivers and stapling instruments for deploying the same
US11877748B2 (en) 2006-10-03 2024-01-23 Cilag Gmbh International Robotically-driven surgical instrument with E-beam driver
US11382626B2 (en) 2006-10-03 2022-07-12 Cilag Gmbh International Surgical system including a knife bar supported for rotational and axial travel
US11844521B2 (en) 2007-01-10 2023-12-19 Cilag Gmbh International Surgical instrument for use with a robotic system
US11937814B2 (en) 2007-01-10 2024-03-26 Cilag Gmbh International Surgical instrument for use with a robotic system
US11000277B2 (en) 2007-01-10 2021-05-11 Ethicon Llc Surgical instrument with wireless communication between control unit and remote sensor
US10945729B2 (en) 2007-01-10 2021-03-16 Ethicon Llc Interlock and surgical instrument including same
US11666332B2 (en) 2007-01-10 2023-06-06 Cilag Gmbh International Surgical instrument comprising a control circuit configured to adjust the operation of a motor
US11134943B2 (en) 2007-01-10 2021-10-05 Cilag Gmbh International Powered surgical instrument including a control unit and sensor
US11812961B2 (en) 2007-01-10 2023-11-14 Cilag Gmbh International Surgical instrument including a motor control system
US11849947B2 (en) 2007-01-10 2023-12-26 Cilag Gmbh International Surgical system including a control circuit and a passively-powered transponder
US11931032B2 (en) 2007-01-10 2024-03-19 Cilag Gmbh International Surgical instrument with wireless communication between a control unit of a robotic system and remote sensor
US11291441B2 (en) 2007-01-10 2022-04-05 Cilag Gmbh International Surgical instrument with wireless communication between control unit and remote sensor
US10918386B2 (en) 2007-01-10 2021-02-16 Ethicon Llc Interlock and surgical instrument including same
US10952727B2 (en) 2007-01-10 2021-03-23 Ethicon Llc Surgical instrument for assessing the state of a staple cartridge
US11350929B2 (en) 2007-01-10 2022-06-07 Cilag Gmbh International Surgical instrument with wireless communication between control unit and sensor transponders
US11166720B2 (en) 2007-01-10 2021-11-09 Cilag Gmbh International Surgical instrument including a control module for assessing an end effector
US11918211B2 (en) 2007-01-10 2024-03-05 Cilag Gmbh International Surgical stapling instrument for use with a robotic system
US11006951B2 (en) 2007-01-10 2021-05-18 Ethicon Llc Surgical instrument with wireless communication between control unit and sensor transponders
US11771426B2 (en) 2007-01-10 2023-10-03 Cilag Gmbh International Surgical instrument with wireless communication
US11839352B2 (en) 2007-01-11 2023-12-12 Cilag Gmbh International Surgical stapling device with an end effector
US11039836B2 (en) 2007-01-11 2021-06-22 Cilag Gmbh International Staple cartridge for use with a surgical stapling instrument
US11337693B2 (en) 2007-03-15 2022-05-24 Cilag Gmbh International Surgical stapling instrument having a releasable buttress material
US10702267B2 (en) 2007-03-15 2020-07-07 Ethicon Llc Surgical stapling instrument having a releasable buttress material
US11134938B2 (en) 2007-06-04 2021-10-05 Cilag Gmbh International Robotically-controlled shaft based rotary drive systems for surgical instruments
US11154298B2 (en) 2007-06-04 2021-10-26 Cilag Gmbh International Stapling system for use with a robotic surgical system
US11147549B2 (en) 2007-06-04 2021-10-19 Cilag Gmbh International Stapling instrument including a firing system and a closure system
US11911028B2 (en) 2007-06-04 2024-02-27 Cilag Gmbh International Surgical instruments for use with a robotic surgical system
US11857181B2 (en) 2007-06-04 2024-01-02 Cilag Gmbh International Robotically-controlled shaft based rotary drive systems for surgical instruments
US11564682B2 (en) 2007-06-04 2023-01-31 Cilag Gmbh International Surgical stapler device
US11672531B2 (en) 2007-06-04 2023-06-13 Cilag Gmbh International Rotary drive systems for surgical instruments
US11559302B2 (en) 2007-06-04 2023-01-24 Cilag Gmbh International Surgical instrument including a firing member movable at different speeds
US11648006B2 (en) 2007-06-04 2023-05-16 Cilag Gmbh International Robotically-controlled shaft based rotary drive systems for surgical instruments
US11013511B2 (en) 2007-06-22 2021-05-25 Ethicon Llc Surgical stapling instrument with an articulatable end effector
US11849941B2 (en) 2007-06-29 2023-12-26 Cilag Gmbh International Staple cartridge having staple cavities extending at a transverse angle relative to a longitudinal cartridge axis
US11925346B2 (en) 2007-06-29 2024-03-12 Cilag Gmbh International Surgical staple cartridge including tissue supporting surfaces
US11464514B2 (en) 2008-02-14 2022-10-11 Cilag Gmbh International Motorized surgical stapling system including a sensing array
US10898194B2 (en) 2008-02-14 2021-01-26 Ethicon Llc Detachable motor powered surgical instrument
US10888330B2 (en) 2008-02-14 2021-01-12 Ethicon Llc Surgical system
US10888329B2 (en) 2008-02-14 2021-01-12 Ethicon Llc Detachable motor powered surgical instrument
US11571212B2 (en) 2008-02-14 2023-02-07 Cilag Gmbh International Surgical stapling system including an impedance sensor
US10925605B2 (en) 2008-02-14 2021-02-23 Ethicon Llc Surgical stapling system
US10639036B2 (en) 2008-02-14 2020-05-05 Ethicon Llc Robotically-controlled motorized surgical cutting and fastening instrument
US10874396B2 (en) 2008-02-14 2020-12-29 Ethicon Llc Stapling instrument for use with a surgical robot
US10660640B2 (en) 2008-02-14 2020-05-26 Ethicon Llc Motorized surgical cutting and fastening instrument
US10682142B2 (en) 2008-02-14 2020-06-16 Ethicon Llc Surgical stapling apparatus including an articulation system
US11801047B2 (en) 2008-02-14 2023-10-31 Cilag Gmbh International Surgical stapling system comprising a control circuit configured to selectively monitor tissue impedance and adjust control of a motor
US11638583B2 (en) 2008-02-14 2023-05-02 Cilag Gmbh International Motorized surgical system having a plurality of power sources
US10806450B2 (en) 2008-02-14 2020-10-20 Ethicon Llc Surgical cutting and fastening instrument having a control system
US10743851B2 (en) 2008-02-14 2020-08-18 Ethicon Llc Interchangeable tools for surgical instruments
US10765432B2 (en) 2008-02-14 2020-09-08 Ethicon Llc Surgical device including a control system
US11484307B2 (en) 2008-02-14 2022-11-01 Cilag Gmbh International Loading unit coupleable to a surgical stapling system
US10716568B2 (en) 2008-02-14 2020-07-21 Ethicon Llc Surgical stapling apparatus with control features operable with one hand
US10898195B2 (en) 2008-02-14 2021-01-26 Ethicon Llc Detachable motor powered surgical instrument
US10722232B2 (en) 2008-02-14 2020-07-28 Ethicon Llc Surgical instrument for use with different cartridges
US11717285B2 (en) 2008-02-14 2023-08-08 Cilag Gmbh International Surgical cutting and fastening instrument having RF electrodes
US10905426B2 (en) 2008-02-14 2021-02-02 Ethicon Llc Detachable motor powered surgical instrument
US11446034B2 (en) 2008-02-14 2022-09-20 Cilag Gmbh International Surgical stapling assembly comprising first and second actuation systems configured to perform different functions
US10743870B2 (en) 2008-02-14 2020-08-18 Ethicon Llc Surgical stapling apparatus with interlockable firing system
US11612395B2 (en) 2008-02-14 2023-03-28 Cilag Gmbh International Surgical system including a control system having an RFID tag reader
US10905427B2 (en) 2008-02-14 2021-02-02 Ethicon Llc Surgical System
US11154297B2 (en) 2008-02-15 2021-10-26 Cilag Gmbh International Layer arrangements for surgical staple cartridges
US11103241B2 (en) 2008-09-23 2021-08-31 Cilag Gmbh International Motor-driven surgical cutting instrument
US11812954B2 (en) 2008-09-23 2023-11-14 Cilag Gmbh International Robotically-controlled motorized surgical instrument with an end effector
US11684361B2 (en) 2008-09-23 2023-06-27 Cilag Gmbh International Motor-driven surgical cutting instrument
US11406380B2 (en) 2008-09-23 2022-08-09 Cilag Gmbh International Motorized surgical instrument
US10980535B2 (en) 2008-09-23 2021-04-20 Ethicon Llc Motorized surgical instrument with an end effector
US11617575B2 (en) 2008-09-23 2023-04-04 Cilag Gmbh International Motor-driven surgical cutting instrument
US11617576B2 (en) 2008-09-23 2023-04-04 Cilag Gmbh International Motor-driven surgical cutting instrument
US11045189B2 (en) 2008-09-23 2021-06-29 Cilag Gmbh International Robotically-controlled motorized surgical instrument with an end effector
US11648005B2 (en) 2008-09-23 2023-05-16 Cilag Gmbh International Robotically-controlled motorized surgical instrument with an end effector
US11871923B2 (en) 2008-09-23 2024-01-16 Cilag Gmbh International Motorized surgical instrument
US10736628B2 (en) 2008-09-23 2020-08-11 Ethicon Llc Motor-driven surgical cutting instrument
US11517304B2 (en) 2008-09-23 2022-12-06 Cilag Gmbh International Motor-driven surgical cutting instrument
US10898184B2 (en) 2008-09-23 2021-01-26 Ethicon Llc Motor-driven surgical cutting instrument
US11583279B2 (en) 2008-10-10 2023-02-21 Cilag Gmbh International Powered surgical cutting and stapling apparatus with manually retractable firing system
US11730477B2 (en) 2008-10-10 2023-08-22 Cilag Gmbh International Powered surgical system with manually retractable firing system
US11793521B2 (en) 2008-10-10 2023-10-24 Cilag Gmbh International Powered surgical cutting and stapling apparatus with manually retractable firing system
US10932778B2 (en) 2008-10-10 2021-03-02 Ethicon Llc Powered surgical cutting and stapling apparatus with manually retractable firing system
US11129615B2 (en) 2009-02-05 2021-09-28 Cilag Gmbh International Surgical stapling system
US11291449B2 (en) 2009-12-24 2022-04-05 Cilag Gmbh International Surgical cutting instrument that analyzes tissue thickness
US10751076B2 (en) 2009-12-24 2020-08-25 Ethicon Llc Motor-driven surgical cutting instrument with electric actuator directional control assembly
US11478247B2 (en) 2010-07-30 2022-10-25 Cilag Gmbh International Tissue acquisition arrangements and methods for surgical stapling devices
US11850310B2 (en) 2010-09-30 2023-12-26 Cilag Gmbh International Staple cartridge including an adjunct
US11911027B2 (en) 2010-09-30 2024-02-27 Cilag Gmbh International Adhesive film laminate
US11857187B2 (en) 2010-09-30 2024-01-02 Cilag Gmbh International Tissue thickness compensator comprising controlled release and expansion
US11559496B2 (en) 2010-09-30 2023-01-24 Cilag Gmbh International Tissue thickness compensator configured to redistribute compressive forces
US10987102B2 (en) 2010-09-30 2021-04-27 Ethicon Llc Tissue thickness compensator comprising a plurality of layers
US11395651B2 (en) 2010-09-30 2022-07-26 Cilag Gmbh International Adhesive film laminate
US11571215B2 (en) 2010-09-30 2023-02-07 Cilag Gmbh International Layer of material for a surgical end effector
US11944292B2 (en) 2010-09-30 2024-04-02 Cilag Gmbh International Anvil layer attached to a proximal end of an end effector
US10898193B2 (en) 2010-09-30 2021-01-26 Ethicon Llc End effector for use with a surgical instrument
US11154296B2 (en) 2010-09-30 2021-10-26 Cilag Gmbh International Anvil layer attached to a proximal end of an end effector
US11540824B2 (en) 2010-09-30 2023-01-03 Cilag Gmbh International Tissue thickness compensator
US11083452B2 (en) 2010-09-30 2021-08-10 Cilag Gmbh International Staple cartridge including a tissue thickness compensator
US10624861B2 (en) 2010-09-30 2020-04-21 Ethicon Llc Tissue thickness compensator configured to redistribute compressive forces
US11925354B2 (en) 2010-09-30 2024-03-12 Cilag Gmbh International Staple cartridge comprising staples positioned within a compressible portion thereof
US11672536B2 (en) 2010-09-30 2023-06-13 Cilag Gmbh International Layer of material for a surgical end effector
US11298125B2 (en) 2010-09-30 2022-04-12 Cilag Gmbh International Tissue stapler having a thickness compensator
US11812965B2 (en) 2010-09-30 2023-11-14 Cilag Gmbh International Layer of material for a surgical end effector
US11406377B2 (en) 2010-09-30 2022-08-09 Cilag Gmbh International Adhesive film laminate
US10835251B2 (en) 2010-09-30 2020-11-17 Ethicon Llc Surgical instrument assembly including an end effector configurable in different positions
US11684360B2 (en) 2010-09-30 2023-06-27 Cilag Gmbh International Staple cartridge comprising a variable thickness compressible portion
US11602340B2 (en) 2010-09-30 2023-03-14 Cilag Gmbh International Adhesive film laminate
US10743877B2 (en) 2010-09-30 2020-08-18 Ethicon Llc Surgical stapler with floating anvil
US10888328B2 (en) 2010-09-30 2021-01-12 Ethicon Llc Surgical end effector
US11737754B2 (en) 2010-09-30 2023-08-29 Cilag Gmbh International Surgical stapler with floating anvil
US10945731B2 (en) 2010-09-30 2021-03-16 Ethicon Llc Tissue thickness compensator comprising controlled release and expansion
US11583277B2 (en) 2010-09-30 2023-02-21 Cilag Gmbh International Layer of material for a surgical end effector
US11883025B2 (en) 2010-09-30 2024-01-30 Cilag Gmbh International Tissue thickness compensator comprising a plurality of layers
US11849952B2 (en) 2010-09-30 2023-12-26 Cilag Gmbh International Staple cartridge comprising staples positioned within a compressible portion thereof
US10695062B2 (en) 2010-10-01 2020-06-30 Ethicon Llc Surgical instrument including a retractable firing member
US11529142B2 (en) 2010-10-01 2022-12-20 Cilag Gmbh International Surgical instrument having a power control circuit
US11504116B2 (en) 2011-04-29 2022-11-22 Cilag Gmbh International Layer of material for a surgical end effector
US11278411B2 (en) 2011-05-26 2022-03-22 Cartiva, Inc. Devices and methods for creating wedge-shaped recesses
US10376368B2 (en) 2011-05-26 2019-08-13 Cartiva, Inc. Devices and methods for creating wedge-shaped recesses
US11944545B2 (en) 2011-05-26 2024-04-02 Cartiva, Inc. Implant introducer
US9526632B2 (en) 2011-05-26 2016-12-27 Cartiva, Inc. Methods of repairing a joint using a wedge-shaped implant
US9155543B2 (en) 2011-05-26 2015-10-13 Cartiva, Inc. Tapered joint implant and related tools
US11266410B2 (en) 2011-05-27 2022-03-08 Cilag Gmbh International Surgical device for use with a robotic system
US10736634B2 (en) 2011-05-27 2020-08-11 Ethicon Llc Robotically-driven surgical instrument including a drive system
US10980534B2 (en) 2011-05-27 2021-04-20 Ethicon Llc Robotically-controlled motorized surgical instrument with an end effector
US11918208B2 (en) 2011-05-27 2024-03-05 Cilag Gmbh International Robotically-controlled shaft based rotary drive systems for surgical instruments
US11612394B2 (en) 2011-05-27 2023-03-28 Cilag Gmbh International Automated end effector component reloading system for use with a robotic system
US11583278B2 (en) 2011-05-27 2023-02-21 Cilag Gmbh International Surgical stapling system having multi-direction articulation
US10813641B2 (en) 2011-05-27 2020-10-27 Ethicon Llc Robotically-driven surgical instrument
US11207064B2 (en) 2011-05-27 2021-12-28 Cilag Gmbh International Automated end effector component reloading system for use with a robotic system
US11129616B2 (en) 2011-05-27 2021-09-28 Cilag Gmbh International Surgical stapling system
US10780539B2 (en) 2011-05-27 2020-09-22 Ethicon Llc Stapling instrument for use with a robotic system
US11439470B2 (en) 2011-05-27 2022-09-13 Cilag Gmbh International Robotically-controlled surgical instrument with selectively articulatable end effector
US11406378B2 (en) 2012-03-28 2022-08-09 Cilag Gmbh International Staple cartridge comprising a compressible tissue thickness compensator
US10667808B2 (en) 2012-03-28 2020-06-02 Ethicon Llc Staple cartridge comprising an absorbable adjunct
US11793509B2 (en) 2012-03-28 2023-10-24 Cilag Gmbh International Staple cartridge including an implantable layer
US11918220B2 (en) 2012-03-28 2024-03-05 Cilag Gmbh International Tissue thickness compensator comprising tissue ingrowth features
US10350072B2 (en) 2012-05-24 2019-07-16 Cartiva, Inc. Tooling for creating tapered opening in tissue and related methods
US11707273B2 (en) 2012-06-15 2023-07-25 Cilag Gmbh International Articulatable surgical instrument comprising a firing drive
US10959725B2 (en) 2012-06-15 2021-03-30 Ethicon Llc Articulatable surgical instrument comprising a firing drive
US11083457B2 (en) 2012-06-28 2021-08-10 Cilag Gmbh International Surgical instrument system including replaceable end effectors
US11857189B2 (en) 2012-06-28 2024-01-02 Cilag Gmbh International Surgical instrument including first and second articulation joints
US11510671B2 (en) 2012-06-28 2022-11-29 Cilag Gmbh International Firing system lockout arrangements for surgical instruments
US11278284B2 (en) 2012-06-28 2022-03-22 Cilag Gmbh International Rotary drive arrangements for surgical instruments
US11039837B2 (en) 2012-06-28 2021-06-22 Cilag Gmbh International Firing system lockout arrangements for surgical instruments
US10687812B2 (en) 2012-06-28 2020-06-23 Ethicon Llc Surgical instrument system including replaceable end effectors
US11779420B2 (en) 2012-06-28 2023-10-10 Cilag Gmbh International Robotic surgical attachments having manually-actuated retraction assemblies
US11058423B2 (en) 2012-06-28 2021-07-13 Cilag Gmbh International Stapling system including first and second closure systems for use with a surgical robot
US11109860B2 (en) 2012-06-28 2021-09-07 Cilag Gmbh International Surgical end effectors for use with hand-held and robotically-controlled rotary powered surgical systems
US11464513B2 (en) 2012-06-28 2022-10-11 Cilag Gmbh International Surgical instrument system including replaceable end effectors
US11602346B2 (en) 2012-06-28 2023-03-14 Cilag Gmbh International Robotically powered surgical device with manually-actuatable reversing system
US11154299B2 (en) 2012-06-28 2021-10-26 Cilag Gmbh International Stapling assembly comprising a firing lockout
US11622766B2 (en) 2012-06-28 2023-04-11 Cilag Gmbh International Empty clip cartridge lockout
US11540829B2 (en) 2012-06-28 2023-01-03 Cilag Gmbh International Surgical instrument system including replaceable end effectors
US10874391B2 (en) 2012-06-28 2020-12-29 Ethicon Llc Surgical instrument system including replaceable end effectors
US11197671B2 (en) 2012-06-28 2021-12-14 Cilag Gmbh International Stapling assembly comprising a lockout
US11534162B2 (en) 2012-06-28 2022-12-27 Cilag GmbH Inlernational Robotically powered surgical device with manually-actuatable reversing system
US11202631B2 (en) 2012-06-28 2021-12-21 Cilag Gmbh International Stapling assembly comprising a firing lockout
US11918213B2 (en) 2012-06-28 2024-03-05 Cilag Gmbh International Surgical stapler including couplers for attaching a shaft to an end effector
US11806013B2 (en) 2012-06-28 2023-11-07 Cilag Gmbh International Firing system arrangements for surgical instruments
US11141156B2 (en) 2012-06-28 2021-10-12 Cilag Gmbh International Surgical stapling assembly comprising flexible output shaft
US11241230B2 (en) 2012-06-28 2022-02-08 Cilag Gmbh International Clip applier tool for use with a robotic surgical system
US10932775B2 (en) 2012-06-28 2021-03-02 Ethicon Llc Firing system lockout arrangements for surgical instruments
US11141155B2 (en) 2012-06-28 2021-10-12 Cilag Gmbh International Drive system for surgical tool
US11373755B2 (en) 2012-08-23 2022-06-28 Cilag Gmbh International Surgical device drive system including a ratchet mechanism
US11529138B2 (en) 2013-03-01 2022-12-20 Cilag Gmbh International Powered surgical instrument including a rotary drive screw
US11246618B2 (en) 2013-03-01 2022-02-15 Cilag Gmbh International Surgical instrument soft stop
US10893867B2 (en) 2013-03-14 2021-01-19 Ethicon Llc Drive train control arrangements for modular surgical instruments
US11266406B2 (en) 2013-03-14 2022-03-08 Cilag Gmbh International Control systems for surgical instruments
US10702266B2 (en) 2013-04-16 2020-07-07 Ethicon Llc Surgical instrument system
US11622763B2 (en) 2013-04-16 2023-04-11 Cilag Gmbh International Stapling assembly comprising a shiftable drive
US10888318B2 (en) 2013-04-16 2021-01-12 Ethicon Llc Powered surgical stapler
US11690615B2 (en) 2013-04-16 2023-07-04 Cilag Gmbh International Surgical system including an electric motor and a surgical instrument
US11395652B2 (en) 2013-04-16 2022-07-26 Cilag Gmbh International Powered surgical stapler
US11564679B2 (en) 2013-04-16 2023-01-31 Cilag Gmbh International Powered surgical stapler
US11638581B2 (en) 2013-04-16 2023-05-02 Cilag Gmbh International Powered surgical stapler
US11633183B2 (en) 2013-04-16 2023-04-25 Cilag International GmbH Stapling assembly comprising a retraction drive
US11406381B2 (en) 2013-04-16 2022-08-09 Cilag Gmbh International Powered surgical stapler
US11000274B2 (en) 2013-08-23 2021-05-11 Ethicon Llc Powered surgical instrument
US10898190B2 (en) 2013-08-23 2021-01-26 Ethicon Llc Secondary battery arrangements for powered surgical instruments
US11109858B2 (en) 2013-08-23 2021-09-07 Cilag Gmbh International Surgical instrument including a display which displays the position of a firing element
US11376001B2 (en) 2013-08-23 2022-07-05 Cilag Gmbh International Surgical stapling device with rotary multi-turn retraction mechanism
US11133106B2 (en) 2013-08-23 2021-09-28 Cilag Gmbh International Surgical instrument assembly comprising a retraction assembly
US11701110B2 (en) 2013-08-23 2023-07-18 Cilag Gmbh International Surgical instrument including a drive assembly movable in a non-motorized mode of operation
US11918209B2 (en) 2013-08-23 2024-03-05 Cilag Gmbh International Torque optimization for surgical instruments
US11134940B2 (en) 2013-08-23 2021-10-05 Cilag Gmbh International Surgical instrument including a variable speed firing member
US11389160B2 (en) 2013-08-23 2022-07-19 Cilag Gmbh International Surgical system comprising a display
US10828032B2 (en) 2013-08-23 2020-11-10 Ethicon Llc End effector detection systems for surgical instruments
US11026680B2 (en) 2013-08-23 2021-06-08 Cilag Gmbh International Surgical instrument configured to operate in different states
US10869665B2 (en) 2013-08-23 2020-12-22 Ethicon Llc Surgical instrument system including a control system
US11504119B2 (en) 2013-08-23 2022-11-22 Cilag Gmbh International Surgical instrument including an electronic firing lockout
US11020115B2 (en) 2014-02-12 2021-06-01 Cilag Gmbh International Deliverable surgical instrument
US11259799B2 (en) 2014-03-26 2022-03-01 Cilag Gmbh International Interface systems for use with surgical instruments
US11497488B2 (en) 2014-03-26 2022-11-15 Cilag Gmbh International Systems and methods for controlling a segmented circuit
US10898185B2 (en) 2014-03-26 2021-01-26 Ethicon Llc Surgical instrument power management through sleep and wake up control
US10863981B2 (en) 2014-03-26 2020-12-15 Ethicon Llc Interface systems for use with surgical instruments
US11382627B2 (en) 2014-04-16 2022-07-12 Cilag Gmbh International Surgical stapling assembly comprising a firing member including a lateral extension
US11266409B2 (en) 2014-04-16 2022-03-08 Cilag Gmbh International Fastener cartridge comprising a sled including longitudinally-staggered ramps
US11883026B2 (en) 2014-04-16 2024-01-30 Cilag Gmbh International Fastener cartridge assemblies and staple retainer cover arrangements
US11298134B2 (en) 2014-04-16 2022-04-12 Cilag Gmbh International Fastener cartridge comprising non-uniform fasteners
US11596406B2 (en) 2014-04-16 2023-03-07 Cilag Gmbh International Fastener cartridges including extensions having different configurations
US11944307B2 (en) 2014-04-16 2024-04-02 Cilag Gmbh International Surgical stapling system including jaw windows
US11717294B2 (en) 2014-04-16 2023-08-08 Cilag Gmbh International End effector arrangements comprising indicators
US11382625B2 (en) 2014-04-16 2022-07-12 Cilag Gmbh International Fastener cartridge comprising non-uniform fasteners
US11918222B2 (en) 2014-04-16 2024-03-05 Cilag Gmbh International Stapling assembly having firing member viewing windows
US11517315B2 (en) 2014-04-16 2022-12-06 Cilag Gmbh International Fastener cartridges including extensions having different configurations
US11925353B2 (en) 2014-04-16 2024-03-12 Cilag Gmbh International Surgical stapling instrument comprising internal passage between stapling cartridge and elongate channel
US10905423B2 (en) 2014-09-05 2021-02-02 Ethicon Llc Smart cartridge wake up operation and data retention
US11311294B2 (en) 2014-09-05 2022-04-26 Cilag Gmbh International Powered medical device including measurement of closure state of jaws
US11653918B2 (en) 2014-09-05 2023-05-23 Cilag Gmbh International Local display of tissue parameter stabilization
US11406386B2 (en) 2014-09-05 2022-08-09 Cilag Gmbh International End effector including magnetic and impedance sensors
US11071545B2 (en) 2014-09-05 2021-07-27 Cilag Gmbh International Smart cartridge wake up operation and data retention
US11389162B2 (en) 2014-09-05 2022-07-19 Cilag Gmbh International Smart cartridge wake up operation and data retention
US11076854B2 (en) 2014-09-05 2021-08-03 Cilag Gmbh International Smart cartridge wake up operation and data retention
US11717297B2 (en) 2014-09-05 2023-08-08 Cilag Gmbh International Smart cartridge wake up operation and data retention
US11284898B2 (en) 2014-09-18 2022-03-29 Cilag Gmbh International Surgical instrument including a deployable knife
US11202633B2 (en) 2014-09-26 2021-12-21 Cilag Gmbh International Surgical stapling buttresses and adjunct materials
US11523821B2 (en) 2014-09-26 2022-12-13 Cilag Gmbh International Method for creating a flexible staple line
US10736630B2 (en) 2014-10-13 2020-08-11 Ethicon Llc Staple cartridge
US11918210B2 (en) 2014-10-16 2024-03-05 Cilag Gmbh International Staple cartridge comprising a cartridge body including a plurality of wells
US11931031B2 (en) 2014-10-16 2024-03-19 Cilag Gmbh International Staple cartridge comprising a deck including an upper surface and a lower surface
US11701114B2 (en) 2014-10-16 2023-07-18 Cilag Gmbh International Staple cartridge
US11185325B2 (en) 2014-10-16 2021-11-30 Cilag Gmbh International End effector including different tissue gaps
US10905418B2 (en) 2014-10-16 2021-02-02 Ethicon Llc Staple cartridge comprising a tissue thickness compensator
US11141153B2 (en) 2014-10-29 2021-10-12 Cilag Gmbh International Staple cartridges comprising driver arrangements
US11457918B2 (en) 2014-10-29 2022-10-04 Cilag Gmbh International Cartridge assemblies for surgical staplers
US11241229B2 (en) 2014-10-29 2022-02-08 Cilag Gmbh International Staple cartridges comprising driver arrangements
US11864760B2 (en) 2014-10-29 2024-01-09 Cilag Gmbh International Staple cartridges comprising driver arrangements
US11931038B2 (en) 2014-10-29 2024-03-19 Cilag Gmbh International Cartridge assemblies for surgical staplers
US11337698B2 (en) 2014-11-06 2022-05-24 Cilag Gmbh International Staple cartridge comprising a releasable adjunct material
US10617417B2 (en) 2014-11-06 2020-04-14 Ethicon Llc Staple cartridge comprising a releasable adjunct material
US10736636B2 (en) 2014-12-10 2020-08-11 Ethicon Llc Articulatable surgical instrument system
US11382628B2 (en) 2014-12-10 2022-07-12 Cilag Gmbh International Articulatable surgical instrument system
US11812958B2 (en) 2014-12-18 2023-11-14 Cilag Gmbh International Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors
US10743873B2 (en) 2014-12-18 2020-08-18 Ethicon Llc Drive arrangements for articulatable surgical instruments
US10695058B2 (en) 2014-12-18 2020-06-30 Ethicon Llc Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member
US11553911B2 (en) 2014-12-18 2023-01-17 Cilag Gmbh International Surgical instrument assembly comprising a flexible articulation system
US11399831B2 (en) 2014-12-18 2022-08-02 Cilag Gmbh International Drive arrangements for articulatable surgical instruments
US10806448B2 (en) 2014-12-18 2020-10-20 Ethicon Llc Surgical instrument assembly comprising a flexible articulation system
US10945728B2 (en) 2014-12-18 2021-03-16 Ethicon Llc Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors
US11547404B2 (en) 2014-12-18 2023-01-10 Cilag Gmbh International Surgical instrument assembly comprising a flexible articulation system
US11547403B2 (en) 2014-12-18 2023-01-10 Cilag Gmbh International Surgical instrument having a laminate firing actuator and lateral buckling supports
US11517311B2 (en) 2014-12-18 2022-12-06 Cilag Gmbh International Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member
US11678877B2 (en) 2014-12-18 2023-06-20 Cilag Gmbh International Surgical instrument including a flexible support configured to support a flexible firing member
US11083453B2 (en) 2014-12-18 2021-08-10 Cilag Gmbh International Surgical stapling system including a flexible firing actuator and lateral buckling supports
US11571207B2 (en) 2014-12-18 2023-02-07 Cilag Gmbh International Surgical system including lateral supports for a flexible drive member
CN107106694B (en) * 2015-01-13 2020-09-22 西格亚有限公司 Process for the preparation of butyric esters of hyaluronic acid sodium salt in water
CN107106694A (en) * 2015-01-13 2017-08-29 西格亚有限公司 The method for being used to prepare the butyric acid ester of hyaluroni in water
US11324506B2 (en) 2015-02-27 2022-05-10 Cilag Gmbh International Modular stapling assembly
US11154301B2 (en) 2015-02-27 2021-10-26 Cilag Gmbh International Modular stapling assembly
US11744588B2 (en) 2015-02-27 2023-09-05 Cilag Gmbh International Surgical stapling instrument including a removably attachable battery pack
US10966627B2 (en) 2015-03-06 2021-04-06 Ethicon Llc Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures
US11350843B2 (en) 2015-03-06 2022-06-07 Cilag Gmbh International Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures
US10617412B2 (en) 2015-03-06 2020-04-14 Ethicon Llc System for detecting the mis-insertion of a staple cartridge into a surgical stapler
US11109859B2 (en) 2015-03-06 2021-09-07 Cilag Gmbh International Surgical instrument comprising a lockable battery housing
US11826132B2 (en) 2015-03-06 2023-11-28 Cilag Gmbh International Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures
US10772625B2 (en) 2015-03-06 2020-09-15 Ethicon Llc Signal and power communication system positioned on a rotatable shaft
US11944338B2 (en) 2015-03-06 2024-04-02 Cilag Gmbh International Multiple level thresholds to modify operation of powered surgical instruments
US11224423B2 (en) 2015-03-06 2022-01-18 Cilag Gmbh International Smart sensors with local signal processing
US10687806B2 (en) 2015-03-06 2020-06-23 Ethicon Llc Adaptive tissue compression techniques to adjust closure rates for multiple tissue types
US11426160B2 (en) 2015-03-06 2022-08-30 Cilag Gmbh International Smart sensors with local signal processing
US11717411B2 (en) 2015-03-31 2023-08-08 Cartiva, Inc. Hydrogel implants with porous materials and methods
US10973644B2 (en) 2015-03-31 2021-04-13 Cartiva, Inc. Hydrogel implants with porous materials and methods
US10758374B2 (en) 2015-03-31 2020-09-01 Cartiva, Inc. Carpometacarpal (CMC) implants and methods
US11918212B2 (en) 2015-03-31 2024-03-05 Cilag Gmbh International Surgical instrument with selectively disengageable drive systems
US9907663B2 (en) 2015-03-31 2018-03-06 Cartiva, Inc. Hydrogel implants with porous materials and methods
US11839552B2 (en) 2015-03-31 2023-12-12 Cartiva, Inc. Carpometacarpal (CMC) implants and methods
US10952858B2 (en) 2015-04-14 2021-03-23 Cartiva, Inc. Tooling for creating tapered opening in tissue and related methods
US11701231B2 (en) 2015-04-14 2023-07-18 Cartiva, Inc. Tooling for creating tapered opening in tissue and related methods
US11020231B2 (en) 2015-04-14 2021-06-01 Cartiva, Inc. Tooling for creating tapered opening in tissue and related methods
US11058425B2 (en) 2015-08-17 2021-07-13 Ethicon Llc Implantable layers for a surgical instrument
US11026678B2 (en) 2015-09-23 2021-06-08 Cilag Gmbh International Surgical stapler having motor control based on an electrical parameter related to a motor current
US11490889B2 (en) 2015-09-23 2022-11-08 Cilag Gmbh International Surgical stapler having motor control based on an electrical parameter related to a motor current
US11344299B2 (en) 2015-09-23 2022-05-31 Cilag Gmbh International Surgical stapler having downstream current-based motor control
US10863986B2 (en) 2015-09-23 2020-12-15 Ethicon Llc Surgical stapler having downstream current-based motor control
US11849946B2 (en) 2015-09-23 2023-12-26 Cilag Gmbh International Surgical stapler having downstream current-based motor control
US11076929B2 (en) 2015-09-25 2021-08-03 Cilag Gmbh International Implantable adjunct systems for determining adjunct skew
US11690623B2 (en) 2015-09-30 2023-07-04 Cilag Gmbh International Method for applying an implantable layer to a fastener cartridge
US11903586B2 (en) 2015-09-30 2024-02-20 Cilag Gmbh International Compressible adjunct with crossing spacer fibers
US11712244B2 (en) 2015-09-30 2023-08-01 Cilag Gmbh International Implantable layer with spacer fibers
US10980539B2 (en) 2015-09-30 2021-04-20 Ethicon Llc Implantable adjunct comprising bonded layers
US11944308B2 (en) 2015-09-30 2024-04-02 Cilag Gmbh International Compressible adjunct with crossing spacer fibers
US10932779B2 (en) 2015-09-30 2021-03-02 Ethicon Llc Compressible adjunct with crossing spacer fibers
US11553916B2 (en) 2015-09-30 2023-01-17 Cilag Gmbh International Compressible adjunct with crossing spacer fibers
US11793522B2 (en) 2015-09-30 2023-10-24 Cilag Gmbh International Staple cartridge assembly including a compressible adjunct
US11890015B2 (en) 2015-09-30 2024-02-06 Cilag Gmbh International Compressible adjunct with crossing spacer fibers
US11759208B2 (en) 2015-12-30 2023-09-19 Cilag Gmbh International Mechanisms for compensating for battery pack failure in powered surgical instruments
US11129613B2 (en) 2015-12-30 2021-09-28 Cilag Gmbh International Surgical instruments with separable motors and motor control circuits
US11484309B2 (en) 2015-12-30 2022-11-01 Cilag Gmbh International Surgical stapling system comprising a controller configured to cause a motor to reset a firing sequence
US11058422B2 (en) 2015-12-30 2021-07-13 Cilag Gmbh International Mechanisms for compensating for battery pack failure in powered surgical instruments
US11083454B2 (en) 2015-12-30 2021-08-10 Cilag Gmbh International Mechanisms for compensating for drivetrain failure in powered surgical instruments
US11213293B2 (en) 2016-02-09 2022-01-04 Cilag Gmbh International Articulatable surgical instruments with single articulation link arrangements
US11523823B2 (en) 2016-02-09 2022-12-13 Cilag Gmbh International Surgical instruments with non-symmetrical articulation arrangements
US11730471B2 (en) 2016-02-09 2023-08-22 Cilag Gmbh International Articulatable surgical instruments with single articulation link arrangements
US11826045B2 (en) 2016-02-12 2023-11-28 Cilag Gmbh International Mechanisms for compensating for drivetrain failure in powered surgical instruments
US11779336B2 (en) 2016-02-12 2023-10-10 Cilag Gmbh International Mechanisms for compensating for drivetrain failure in powered surgical instruments
US11344303B2 (en) 2016-02-12 2022-05-31 Cilag Gmbh International Mechanisms for compensating for drivetrain failure in powered surgical instruments
US11224426B2 (en) 2016-02-12 2022-01-18 Cilag Gmbh International Mechanisms for compensating for drivetrain failure in powered surgical instruments
US11311292B2 (en) 2016-04-15 2022-04-26 Cilag Gmbh International Surgical instrument with detection sensors
US11642125B2 (en) 2016-04-15 2023-05-09 Cilag Gmbh International Robotic surgical system including a user interface and a control circuit
US11026684B2 (en) 2016-04-15 2021-06-08 Ethicon Llc Surgical instrument with multiple program responses during a firing motion
US11317910B2 (en) 2016-04-15 2022-05-03 Cilag Gmbh International Surgical instrument with detection sensors
US11931028B2 (en) 2016-04-15 2024-03-19 Cilag Gmbh International Surgical instrument with multiple program responses during a firing motion
US11051810B2 (en) 2016-04-15 2021-07-06 Cilag Gmbh International Modular surgical instrument with configurable operating mode
US11350932B2 (en) 2016-04-15 2022-06-07 Cilag Gmbh International Surgical instrument with improved stop/start control during a firing motion
US11284891B2 (en) 2016-04-15 2022-03-29 Cilag Gmbh International Surgical instrument with multiple program responses during a firing motion
US11517306B2 (en) 2016-04-15 2022-12-06 Cilag Gmbh International Surgical instrument with detection sensors
US11607239B2 (en) 2016-04-15 2023-03-21 Cilag Gmbh International Systems and methods for controlling a surgical stapling and cutting instrument
US11179150B2 (en) 2016-04-15 2021-11-23 Cilag Gmbh International Systems and methods for controlling a surgical stapling and cutting instrument
US11191545B2 (en) 2016-04-15 2021-12-07 Cilag Gmbh International Staple formation detection mechanisms
US11147554B2 (en) 2016-04-18 2021-10-19 Cilag Gmbh International Surgical instrument system comprising a magnetic lockout
US11559303B2 (en) 2016-04-18 2023-01-24 Cilag Gmbh International Cartridge lockout arrangements for rotary powered surgical cutting and stapling instruments
US11350928B2 (en) 2016-04-18 2022-06-07 Cilag Gmbh International Surgical instrument comprising a tissue thickness lockout and speed control system
US11811253B2 (en) 2016-04-18 2023-11-07 Cilag Gmbh International Surgical robotic system with fault state detection configurations based on motor current draw
US11317917B2 (en) 2016-04-18 2022-05-03 Cilag Gmbh International Surgical stapling system comprising a lockable firing assembly
US11931034B2 (en) 2016-12-21 2024-03-19 Cilag Gmbh International Surgical stapling instruments with smart staple cartridges
US11766259B2 (en) 2016-12-21 2023-09-26 Cilag Gmbh International Method of deforming staples from two different types of staple cartridges with the same surgical stapling instrument
US11653917B2 (en) 2016-12-21 2023-05-23 Cilag Gmbh International Surgical stapling systems
US10881401B2 (en) 2016-12-21 2021-01-05 Ethicon Llc Staple firing member comprising a missing cartridge and/or spent cartridge lockout
US10610224B2 (en) 2016-12-21 2020-04-07 Ethicon Llc Lockout arrangements for surgical end effectors and replaceable tool assemblies
US10888322B2 (en) 2016-12-21 2021-01-12 Ethicon Llc Surgical instrument comprising a cutting member
US11369376B2 (en) 2016-12-21 2022-06-28 Cilag Gmbh International Surgical stapling systems
US11191543B2 (en) 2016-12-21 2021-12-07 Cilag Gmbh International Assembly comprising a lock
US10687809B2 (en) 2016-12-21 2020-06-23 Ethicon Llc Surgical staple cartridge with movable camming member configured to disengage firing member lockout features
US11497499B2 (en) 2016-12-21 2022-11-15 Cilag Gmbh International Articulatable surgical stapling instruments
US11191540B2 (en) 2016-12-21 2021-12-07 Cilag Gmbh International Protective cover arrangements for a joint interface between a movable jaw and actuator shaft of a surgical instrument
US10893864B2 (en) 2016-12-21 2021-01-19 Ethicon Staple cartridges and arrangements of staples and staple cavities therein
US10898186B2 (en) 2016-12-21 2021-01-26 Ethicon Llc Staple forming pocket arrangements comprising primary sidewalls and pocket sidewalls
US11191539B2 (en) 2016-12-21 2021-12-07 Cilag Gmbh International Shaft assembly comprising a manually-operable retraction system for use with a motorized surgical instrument system
US10682138B2 (en) 2016-12-21 2020-06-16 Ethicon Llc Bilaterally asymmetric staple forming pocket pairs
US10779823B2 (en) 2016-12-21 2020-09-22 Ethicon Llc Firing member pin angle
US10905422B2 (en) 2016-12-21 2021-02-02 Ethicon Llc Surgical instrument for use with a robotic surgical system
US10667809B2 (en) 2016-12-21 2020-06-02 Ethicon Llc Staple cartridge and staple cartridge channel comprising windows defined therein
US11179155B2 (en) 2016-12-21 2021-11-23 Cilag Gmbh International Anvil arrangements for surgical staplers
US11701115B2 (en) 2016-12-21 2023-07-18 Cilag Gmbh International Methods of stapling tissue
US11350935B2 (en) 2016-12-21 2022-06-07 Cilag Gmbh International Surgical tool assemblies with closure stroke reduction features
US11350934B2 (en) 2016-12-21 2022-06-07 Cilag Gmbh International Staple forming pocket arrangement to accommodate different types of staples
US11224428B2 (en) 2016-12-21 2022-01-18 Cilag Gmbh International Surgical stapling systems
US11160553B2 (en) 2016-12-21 2021-11-02 Cilag Gmbh International Surgical stapling systems
US10856868B2 (en) 2016-12-21 2020-12-08 Ethicon Llc Firing member pin configurations
US11918215B2 (en) 2016-12-21 2024-03-05 Cilag Gmbh International Staple cartridge with array of staple pockets
US10758230B2 (en) 2016-12-21 2020-09-01 Ethicon Llc Surgical instrument with primary and safety processors
US11317913B2 (en) 2016-12-21 2022-05-03 Cilag Gmbh International Lockout arrangements for surgical end effectors and replaceable tool assemblies
US11134942B2 (en) 2016-12-21 2021-10-05 Cilag Gmbh International Surgical stapling instruments and staple-forming anvils
US10695055B2 (en) 2016-12-21 2020-06-30 Ethicon Llc Firing assembly comprising a lockout
US10959727B2 (en) 2016-12-21 2021-03-30 Ethicon Llc Articulatable surgical end effector with asymmetric shaft arrangement
US11160551B2 (en) 2016-12-21 2021-11-02 Cilag Gmbh International Articulatable surgical stapling instruments
US10758229B2 (en) 2016-12-21 2020-09-01 Ethicon Llc Surgical instrument comprising improved jaw control
US11849948B2 (en) 2016-12-21 2023-12-26 Cilag Gmbh International Method for resetting a fuse of a surgical instrument shaft
US11419606B2 (en) 2016-12-21 2022-08-23 Cilag Gmbh International Shaft assembly comprising a clutch configured to adapt the output of a rotary firing member to two different systems
US11096689B2 (en) 2016-12-21 2021-08-24 Cilag Gmbh International Shaft assembly comprising a lockout
US11571210B2 (en) 2016-12-21 2023-02-07 Cilag Gmbh International Firing assembly comprising a multiple failed-state fuse
US11564688B2 (en) 2016-12-21 2023-01-31 Cilag Gmbh International Robotic surgical tool having a retraction mechanism
US10973516B2 (en) 2016-12-21 2021-04-13 Ethicon Llc Surgical end effectors and adaptable firing members therefor
US11090048B2 (en) 2016-12-21 2021-08-17 Cilag Gmbh International Method for resetting a fuse of a surgical instrument shaft
US10639035B2 (en) 2016-12-21 2020-05-05 Ethicon Llc Surgical stapling instruments and replaceable tool assemblies thereof
US11766260B2 (en) 2016-12-21 2023-09-26 Cilag Gmbh International Methods of stapling tissue
US11071554B2 (en) 2017-06-20 2021-07-27 Cilag Gmbh International Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on magnitude of velocity error measurements
US11793513B2 (en) 2017-06-20 2023-10-24 Cilag Gmbh International Systems and methods for controlling motor speed according to user input for a surgical instrument
US11871939B2 (en) 2017-06-20 2024-01-16 Cilag Gmbh International Method for closed loop control of motor velocity of a surgical stapling and cutting instrument
US11213302B2 (en) 2017-06-20 2022-01-04 Cilag Gmbh International Method for closed loop control of motor velocity of a surgical stapling and cutting instrument
US11517325B2 (en) 2017-06-20 2022-12-06 Cilag Gmbh International Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured displacement distance traveled over a specified time interval
US10980537B2 (en) 2017-06-20 2021-04-20 Ethicon Llc Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified number of shaft rotations
US11672532B2 (en) 2017-06-20 2023-06-13 Cilag Gmbh International Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument
US10881399B2 (en) 2017-06-20 2021-01-05 Ethicon Llc Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument
US11090046B2 (en) 2017-06-20 2021-08-17 Cilag Gmbh International Systems and methods for controlling displacement member motion of a surgical stapling and cutting instrument
US11653914B2 (en) 2017-06-20 2023-05-23 Cilag Gmbh International Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument according to articulation angle of end effector
US10646220B2 (en) 2017-06-20 2020-05-12 Ethicon Llc Systems and methods for controlling displacement member velocity for a surgical instrument
US10779820B2 (en) 2017-06-20 2020-09-22 Ethicon Llc Systems and methods for controlling motor speed according to user input for a surgical instrument
USD890784S1 (en) 2017-06-20 2020-07-21 Ethicon Llc Display panel with changeable graphical user interface
US10888321B2 (en) 2017-06-20 2021-01-12 Ethicon Llc Systems and methods for controlling velocity of a displacement member of a surgical stapling and cutting instrument
US11382638B2 (en) 2017-06-20 2022-07-12 Cilag Gmbh International Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified displacement distance
US11266405B2 (en) 2017-06-27 2022-03-08 Cilag Gmbh International Surgical anvil manufacturing methods
US10993716B2 (en) 2017-06-27 2021-05-04 Ethicon Llc Surgical anvil arrangements
US11766258B2 (en) 2017-06-27 2023-09-26 Cilag Gmbh International Surgical anvil arrangements
US11090049B2 (en) 2017-06-27 2021-08-17 Cilag Gmbh International Staple forming pocket arrangements
US10631859B2 (en) 2017-06-27 2020-04-28 Ethicon Llc Articulation systems for surgical instruments
US11141154B2 (en) 2017-06-27 2021-10-12 Cilag Gmbh International Surgical end effectors and anvils
US11324503B2 (en) 2017-06-27 2022-05-10 Cilag Gmbh International Surgical firing member arrangements
US10856869B2 (en) 2017-06-27 2020-12-08 Ethicon Llc Surgical anvil arrangements
US11826048B2 (en) 2017-06-28 2023-11-28 Cilag Gmbh International Surgical instrument comprising selectively actuatable rotatable couplers
US11058424B2 (en) 2017-06-28 2021-07-13 Cilag Gmbh International Surgical instrument comprising an offset articulation joint
US11529140B2 (en) 2017-06-28 2022-12-20 Cilag Gmbh International Surgical instrument lockout arrangement
US11678880B2 (en) 2017-06-28 2023-06-20 Cilag Gmbh International Surgical instrument comprising a shaft including a housing arrangement
US11564686B2 (en) 2017-06-28 2023-01-31 Cilag Gmbh International Surgical shaft assemblies with flexible interfaces
USD906355S1 (en) 2017-06-28 2020-12-29 Ethicon Llc Display screen or portion thereof with a graphical user interface for a surgical instrument
US10758232B2 (en) 2017-06-28 2020-09-01 Ethicon Llc Surgical instrument with positive jaw opening features
US10716614B2 (en) 2017-06-28 2020-07-21 Ethicon Llc Surgical shaft assemblies with slip ring assemblies with increased contact pressure
US11083455B2 (en) 2017-06-28 2021-08-10 Cilag Gmbh International Surgical instrument comprising an articulation system ratio
US11696759B2 (en) 2017-06-28 2023-07-11 Cilag Gmbh International Surgical stapling instruments comprising shortened staple cartridge noses
US11478242B2 (en) 2017-06-28 2022-10-25 Cilag Gmbh International Jaw retainer arrangement for retaining a pivotable surgical instrument jaw in pivotable retaining engagement with a second surgical instrument jaw
US11259805B2 (en) 2017-06-28 2022-03-01 Cilag Gmbh International Surgical instrument comprising firing member supports
US11020114B2 (en) 2017-06-28 2021-06-01 Cilag Gmbh International Surgical instruments with articulatable end effector with axially shortened articulation joint configurations
US10765427B2 (en) 2017-06-28 2020-09-08 Ethicon Llc Method for articulating a surgical instrument
USD1018577S1 (en) 2017-06-28 2024-03-19 Cilag Gmbh International Display screen or portion thereof with a graphical user interface for a surgical instrument
US10695057B2 (en) 2017-06-28 2020-06-30 Ethicon Llc Surgical instrument lockout arrangement
US10779824B2 (en) 2017-06-28 2020-09-22 Ethicon Llc Surgical instrument comprising an articulation system lockable by a closure system
US10903685B2 (en) 2017-06-28 2021-01-26 Ethicon Llc Surgical shaft assemblies with slip ring assemblies forming capacitive channels
US11246592B2 (en) 2017-06-28 2022-02-15 Cilag Gmbh International Surgical instrument comprising an articulation system lockable to a frame
US11389161B2 (en) 2017-06-28 2022-07-19 Cilag Gmbh International Surgical instrument comprising selectively actuatable rotatable couplers
US11642128B2 (en) 2017-06-28 2023-05-09 Cilag Gmbh International Method for articulating a surgical instrument
US11000279B2 (en) 2017-06-28 2021-05-11 Ethicon Llc Surgical instrument comprising an articulation system ratio
US10786253B2 (en) 2017-06-28 2020-09-29 Ethicon Llc Surgical end effectors with improved jaw aperture arrangements
US11484310B2 (en) 2017-06-28 2022-11-01 Cilag Gmbh International Surgical instrument comprising a shaft including a closure tube profile
US10898183B2 (en) 2017-06-29 2021-01-26 Ethicon Llc Robotic surgical instrument with closed loop feedback techniques for advancement of closure member during firing
US10932772B2 (en) 2017-06-29 2021-03-02 Ethicon Llc Methods for closed loop velocity control for robotic surgical instrument
US11007022B2 (en) 2017-06-29 2021-05-18 Ethicon Llc Closed loop velocity control techniques based on sensed tissue parameters for robotic surgical instrument
US11890005B2 (en) 2017-06-29 2024-02-06 Cilag Gmbh International Methods for closed loop velocity control for robotic surgical instrument
US11471155B2 (en) 2017-08-03 2022-10-18 Cilag Gmbh International Surgical system bailout
US11944300B2 (en) 2017-08-03 2024-04-02 Cilag Gmbh International Method for operating a surgical system bailout
US11304695B2 (en) 2017-08-03 2022-04-19 Cilag Gmbh International Surgical system shaft interconnection
US11399829B2 (en) 2017-09-29 2022-08-02 Cilag Gmbh International Systems and methods of initiating a power shutdown mode for a surgical instrument
US10765429B2 (en) 2017-09-29 2020-09-08 Ethicon Llc Systems and methods for providing alerts according to the operational state of a surgical instrument
USD907648S1 (en) 2017-09-29 2021-01-12 Ethicon Llc Display screen or portion thereof with animated graphical user interface
USD917500S1 (en) 2017-09-29 2021-04-27 Ethicon Llc Display screen or portion thereof with graphical user interface
US10743872B2 (en) 2017-09-29 2020-08-18 Ethicon Llc System and methods for controlling a display of a surgical instrument
USD907647S1 (en) 2017-09-29 2021-01-12 Ethicon Llc Display screen or portion thereof with animated graphical user interface
US11134944B2 (en) 2017-10-30 2021-10-05 Cilag Gmbh International Surgical stapler knife motion controls
US11090075B2 (en) 2017-10-30 2021-08-17 Cilag Gmbh International Articulation features for surgical end effector
US10779903B2 (en) 2017-10-31 2020-09-22 Ethicon Llc Positive shaft rotation lock activated by jaw closure
US10842490B2 (en) 2017-10-31 2020-11-24 Ethicon Llc Cartridge body design with force reduction based on firing completion
US11478244B2 (en) 2017-10-31 2022-10-25 Cilag Gmbh International Cartridge body design with force reduction based on firing completion
US11071543B2 (en) 2017-12-15 2021-07-27 Cilag Gmbh International Surgical end effectors with clamping assemblies configured to increase jaw aperture ranges
US11033267B2 (en) 2017-12-15 2021-06-15 Ethicon Llc Systems and methods of controlling a clamping member firing rate of a surgical instrument
US10687813B2 (en) 2017-12-15 2020-06-23 Ethicon Llc Adapters with firing stroke sensing arrangements for use in connection with electromechanical surgical instruments
US10779826B2 (en) 2017-12-15 2020-09-22 Ethicon Llc Methods of operating surgical end effectors
US10743875B2 (en) 2017-12-15 2020-08-18 Ethicon Llc Surgical end effectors with jaw stiffener arrangements configured to permit monitoring of firing member
US10966718B2 (en) 2017-12-15 2021-04-06 Ethicon Llc Dynamic clamping assemblies with improved wear characteristics for use in connection with electromechanical surgical instruments
US11006955B2 (en) 2017-12-15 2021-05-18 Ethicon Llc End effectors with positive jaw opening features for use with adapters for electromechanical surgical instruments
US10869666B2 (en) 2017-12-15 2020-12-22 Ethicon Llc Adapters with control systems for controlling multiple motors of an electromechanical surgical instrument
US11896222B2 (en) 2017-12-15 2024-02-13 Cilag Gmbh International Methods of operating surgical end effectors
US10779825B2 (en) 2017-12-15 2020-09-22 Ethicon Llc Adapters with end effector position sensing and control arrangements for use in connection with electromechanical surgical instruments
US11197670B2 (en) 2017-12-15 2021-12-14 Cilag Gmbh International Surgical end effectors with pivotal jaws configured to touch at their respective distal ends when fully closed
US10743874B2 (en) 2017-12-15 2020-08-18 Ethicon Llc Sealed adapters for use with electromechanical surgical instruments
US10828033B2 (en) 2017-12-15 2020-11-10 Ethicon Llc Handheld electromechanical surgical instruments with improved motor control arrangements for positioning components of an adapter coupled thereto
US10716565B2 (en) 2017-12-19 2020-07-21 Ethicon Llc Surgical instruments with dual articulation drivers
US10729509B2 (en) 2017-12-19 2020-08-04 Ethicon Llc Surgical instrument comprising closure and firing locking mechanism
USD910847S1 (en) 2017-12-19 2021-02-16 Ethicon Llc Surgical instrument assembly
US11284953B2 (en) 2017-12-19 2022-03-29 Cilag Gmbh International Method for determining the position of a rotatable jaw of a surgical instrument attachment assembly
US10835330B2 (en) 2017-12-19 2020-11-17 Ethicon Llc Method for determining the position of a rotatable jaw of a surgical instrument attachment assembly
US11045270B2 (en) 2017-12-19 2021-06-29 Cilag Gmbh International Robotic attachment comprising exterior drive actuator
US11020112B2 (en) 2017-12-19 2021-06-01 Ethicon Llc Surgical tools configured for interchangeable use with different controller interfaces
US11179152B2 (en) 2017-12-21 2021-11-23 Cilag Gmbh International Surgical instrument comprising a tissue grasping system
US11751867B2 (en) 2017-12-21 2023-09-12 Cilag Gmbh International Surgical instrument comprising sequenced systems
US10682134B2 (en) 2017-12-21 2020-06-16 Ethicon Llc Continuous use self-propelled stapling instrument
US11576668B2 (en) 2017-12-21 2023-02-14 Cilag Gmbh International Staple instrument comprising a firing path display
US10743868B2 (en) 2017-12-21 2020-08-18 Ethicon Llc Surgical instrument comprising a pivotable distal head
US11311290B2 (en) 2017-12-21 2022-04-26 Cilag Gmbh International Surgical instrument comprising an end effector dampener
US11583274B2 (en) 2017-12-21 2023-02-21 Cilag Gmbh International Self-guiding stapling instrument
US11849939B2 (en) 2017-12-21 2023-12-26 Cilag Gmbh International Continuous use self-propelled stapling instrument
US11129680B2 (en) 2017-12-21 2021-09-28 Cilag Gmbh International Surgical instrument comprising a projector
US11337691B2 (en) 2017-12-21 2022-05-24 Cilag Gmbh International Surgical instrument configured to determine firing path
US11364027B2 (en) 2017-12-21 2022-06-21 Cilag Gmbh International Surgical instrument comprising speed control
US11076853B2 (en) 2017-12-21 2021-08-03 Cilag Gmbh International Systems and methods of displaying a knife position during transection for a surgical instrument
US11883019B2 (en) 2017-12-21 2024-01-30 Cilag Gmbh International Stapling instrument comprising a staple feeding system
US11369368B2 (en) 2017-12-21 2022-06-28 Cilag Gmbh International Surgical instrument comprising synchronized drive systems
US11179151B2 (en) 2017-12-21 2021-11-23 Cilag Gmbh International Surgical instrument comprising a display
US11207065B2 (en) 2018-08-20 2021-12-28 Cilag Gmbh International Method for fabricating surgical stapler anvils
US10779821B2 (en) 2018-08-20 2020-09-22 Ethicon Llc Surgical stapler anvils with tissue stop features configured to avoid tissue pinch
US10842492B2 (en) 2018-08-20 2020-11-24 Ethicon Llc Powered articulatable surgical instruments with clutching and locking arrangements for linking an articulation drive system to a firing drive system
US10856870B2 (en) 2018-08-20 2020-12-08 Ethicon Llc Switching arrangements for motor powered articulatable surgical instruments
US11039834B2 (en) 2018-08-20 2021-06-22 Cilag Gmbh International Surgical stapler anvils with staple directing protrusions and tissue stability features
USD914878S1 (en) 2018-08-20 2021-03-30 Ethicon Llc Surgical instrument anvil
US11291440B2 (en) 2018-08-20 2022-04-05 Cilag Gmbh International Method for operating a powered articulatable surgical instrument
US11253256B2 (en) 2018-08-20 2022-02-22 Cilag Gmbh International Articulatable motor powered surgical instruments with dedicated articulation motor arrangements
US11083458B2 (en) 2018-08-20 2021-08-10 Cilag Gmbh International Powered surgical instruments with clutching arrangements to convert linear drive motions to rotary drive motions
US10912559B2 (en) 2018-08-20 2021-02-09 Ethicon Llc Reinforced deformable anvil tip for surgical stapler anvil
US11045192B2 (en) 2018-08-20 2021-06-29 Cilag Gmbh International Fabricating techniques for surgical stapler anvils
US11324501B2 (en) 2018-08-20 2022-05-10 Cilag Gmbh International Surgical stapling devices with improved closure members
US11147553B2 (en) 2019-03-25 2021-10-19 Cilag Gmbh International Firing drive arrangements for surgical systems
US11147551B2 (en) 2019-03-25 2021-10-19 Cilag Gmbh International Firing drive arrangements for surgical systems
US11696761B2 (en) 2019-03-25 2023-07-11 Cilag Gmbh International Firing drive arrangements for surgical systems
US11172929B2 (en) 2019-03-25 2021-11-16 Cilag Gmbh International Articulation drive arrangements for surgical systems
US11253254B2 (en) 2019-04-30 2022-02-22 Cilag Gmbh International Shaft rotation actuator on a surgical instrument
US11452528B2 (en) 2019-04-30 2022-09-27 Cilag Gmbh International Articulation actuators for a surgical instrument
US11903581B2 (en) 2019-04-30 2024-02-20 Cilag Gmbh International Methods for stapling tissue using a surgical instrument
US11426251B2 (en) 2019-04-30 2022-08-30 Cilag Gmbh International Articulation directional lights on a surgical instrument
US11432816B2 (en) 2019-04-30 2022-09-06 Cilag Gmbh International Articulation pin for a surgical instrument
US11471157B2 (en) 2019-04-30 2022-10-18 Cilag Gmbh International Articulation control mapping for a surgical instrument
US11648009B2 (en) 2019-04-30 2023-05-16 Cilag Gmbh International Rotatable jaw tip for a surgical instrument
US11426167B2 (en) 2019-06-28 2022-08-30 Cilag Gmbh International Mechanisms for proper anvil attachment surgical stapling head assembly
US11523822B2 (en) 2019-06-28 2022-12-13 Cilag Gmbh International Battery pack including a circuit interrupter
US11684369B2 (en) 2019-06-28 2023-06-27 Cilag Gmbh International Method of using multiple RFID chips with a surgical assembly
US11684434B2 (en) 2019-06-28 2023-06-27 Cilag Gmbh International Surgical RFID assemblies for instrument operational setting control
US11376098B2 (en) 2019-06-28 2022-07-05 Cilag Gmbh International Surgical instrument system comprising an RFID system
US11464601B2 (en) 2019-06-28 2022-10-11 Cilag Gmbh International Surgical instrument comprising an RFID system for tracking a movable component
US11219455B2 (en) 2019-06-28 2022-01-11 Cilag Gmbh International Surgical instrument including a lockout key
US11638587B2 (en) 2019-06-28 2023-05-02 Cilag Gmbh International RFID identification systems for surgical instruments
US11553971B2 (en) 2019-06-28 2023-01-17 Cilag Gmbh International Surgical RFID assemblies for display and communication
US11224497B2 (en) 2019-06-28 2022-01-18 Cilag Gmbh International Surgical systems with multiple RFID tags
US11229437B2 (en) 2019-06-28 2022-01-25 Cilag Gmbh International Method for authenticating the compatibility of a staple cartridge with a surgical instrument
US11553919B2 (en) 2019-06-28 2023-01-17 Cilag Gmbh International Method for authenticating the compatibility of a staple cartridge with a surgical instrument
US11241235B2 (en) 2019-06-28 2022-02-08 Cilag Gmbh International Method of using multiple RFID chips with a surgical assembly
US11497492B2 (en) 2019-06-28 2022-11-15 Cilag Gmbh International Surgical instrument including an articulation lock
US11246678B2 (en) 2019-06-28 2022-02-15 Cilag Gmbh International Surgical stapling system having a frangible RFID tag
US11350938B2 (en) 2019-06-28 2022-06-07 Cilag Gmbh International Surgical instrument comprising an aligned rfid sensor
US11259803B2 (en) 2019-06-28 2022-03-01 Cilag Gmbh International Surgical stapling system having an information encryption protocol
US11627959B2 (en) 2019-06-28 2023-04-18 Cilag Gmbh International Surgical instruments including manual and powered system lockouts
US11051807B2 (en) 2019-06-28 2021-07-06 Cilag Gmbh International Packaging assembly including a particulate trap
US11478241B2 (en) 2019-06-28 2022-10-25 Cilag Gmbh International Staple cartridge including projections
US11771419B2 (en) 2019-06-28 2023-10-03 Cilag Gmbh International Packaging for a replaceable component of a surgical stapling system
US11291451B2 (en) 2019-06-28 2022-04-05 Cilag Gmbh International Surgical instrument with battery compatibility verification functionality
US11298132B2 (en) 2019-06-28 2022-04-12 Cilag GmbH Inlernational Staple cartridge including a honeycomb extension
US11298127B2 (en) 2019-06-28 2022-04-12 Cilag GmbH Interational Surgical stapling system having a lockout mechanism for an incompatible cartridge
US11744593B2 (en) 2019-06-28 2023-09-05 Cilag Gmbh International Method for authenticating the compatibility of a staple cartridge with a surgical instrument
US11660163B2 (en) 2019-06-28 2023-05-30 Cilag Gmbh International Surgical system with RFID tags for updating motor assembly parameters
US11399837B2 (en) 2019-06-28 2022-08-02 Cilag Gmbh International Mechanisms for motor control adjustments of a motorized surgical instrument
US11464512B2 (en) 2019-12-19 2022-10-11 Cilag Gmbh International Staple cartridge comprising a curved deck surface
US11234698B2 (en) 2019-12-19 2022-02-01 Cilag Gmbh International Stapling system comprising a clamp lockout and a firing lockout
US11529139B2 (en) 2019-12-19 2022-12-20 Cilag Gmbh International Motor driven surgical instrument
US11844520B2 (en) 2019-12-19 2023-12-19 Cilag Gmbh International Staple cartridge comprising driver retention members
US11529137B2 (en) 2019-12-19 2022-12-20 Cilag Gmbh International Staple cartridge comprising driver retention members
US11576672B2 (en) 2019-12-19 2023-02-14 Cilag Gmbh International Surgical instrument comprising a closure system including a closure member and an opening member driven by a drive screw
US11559304B2 (en) 2019-12-19 2023-01-24 Cilag Gmbh International Surgical instrument comprising a rapid closure mechanism
US11911032B2 (en) 2019-12-19 2024-02-27 Cilag Gmbh International Staple cartridge comprising a seating cam
US11701111B2 (en) 2019-12-19 2023-07-18 Cilag Gmbh International Method for operating a surgical stapling instrument
US11607219B2 (en) 2019-12-19 2023-03-21 Cilag Gmbh International Staple cartridge comprising a detachable tissue cutting knife
US11304696B2 (en) 2019-12-19 2022-04-19 Cilag Gmbh International Surgical instrument comprising a powered articulation system
US11931033B2 (en) 2019-12-19 2024-03-19 Cilag Gmbh International Staple cartridge comprising a latch lockout
US11446029B2 (en) 2019-12-19 2022-09-20 Cilag Gmbh International Staple cartridge comprising projections extending from a curved deck surface
US11291447B2 (en) 2019-12-19 2022-04-05 Cilag Gmbh International Stapling instrument comprising independent jaw closing and staple firing systems
US11504122B2 (en) 2019-12-19 2022-11-22 Cilag Gmbh International Surgical instrument comprising a nested firing member
USD976401S1 (en) 2020-06-02 2023-01-24 Cilag Gmbh International Staple cartridge
USD975851S1 (en) 2020-06-02 2023-01-17 Cilag Gmbh International Staple cartridge
USD975278S1 (en) 2020-06-02 2023-01-10 Cilag Gmbh International Staple cartridge
USD974560S1 (en) 2020-06-02 2023-01-03 Cilag Gmbh International Staple cartridge
USD967421S1 (en) 2020-06-02 2022-10-18 Cilag Gmbh International Staple cartridge
USD966512S1 (en) 2020-06-02 2022-10-11 Cilag Gmbh International Staple cartridge
USD975850S1 (en) 2020-06-02 2023-01-17 Cilag Gmbh International Staple cartridge
US11857182B2 (en) 2020-07-28 2024-01-02 Cilag Gmbh International Surgical instruments with combination function articulation joint arrangements
US11826013B2 (en) 2020-07-28 2023-11-28 Cilag Gmbh International Surgical instruments with firing member closure features
US11864756B2 (en) 2020-07-28 2024-01-09 Cilag Gmbh International Surgical instruments with flexible ball chain drive arrangements
US11871925B2 (en) 2020-07-28 2024-01-16 Cilag Gmbh International Surgical instruments with dual spherical articulation joint arrangements
US11660090B2 (en) 2020-07-28 2023-05-30 Cllag GmbH International Surgical instruments with segmented flexible drive arrangements
US11883024B2 (en) 2020-07-28 2024-01-30 Cilag Gmbh International Method of operating a surgical instrument
US11737748B2 (en) 2020-07-28 2023-08-29 Cilag Gmbh International Surgical instruments with double spherical articulation joints with pivotable links
US11638582B2 (en) 2020-07-28 2023-05-02 Cilag Gmbh International Surgical instruments with torsion spine drive arrangements
US11896217B2 (en) 2020-10-29 2024-02-13 Cilag Gmbh International Surgical instrument comprising an articulation lock
US11844518B2 (en) 2020-10-29 2023-12-19 Cilag Gmbh International Method for operating a surgical instrument
USD980425S1 (en) 2020-10-29 2023-03-07 Cilag Gmbh International Surgical instrument assembly
USD1013170S1 (en) 2020-10-29 2024-01-30 Cilag Gmbh International Surgical instrument assembly
US11534259B2 (en) 2020-10-29 2022-12-27 Cilag Gmbh International Surgical instrument comprising an articulation indicator
US11931025B2 (en) 2020-10-29 2024-03-19 Cilag Gmbh International Surgical instrument comprising a releasable closure drive lock
US11617577B2 (en) 2020-10-29 2023-04-04 Cilag Gmbh International Surgical instrument comprising a sensor configured to sense whether an articulation drive of the surgical instrument is actuatable
US11452526B2 (en) 2020-10-29 2022-09-27 Cilag Gmbh International Surgical instrument comprising a staged voltage regulation start-up system
US11717289B2 (en) 2020-10-29 2023-08-08 Cilag Gmbh International Surgical instrument comprising an indicator which indicates that an articulation drive is actuatable
US11779330B2 (en) 2020-10-29 2023-10-10 Cilag Gmbh International Surgical instrument comprising a jaw alignment system
US11517390B2 (en) 2020-10-29 2022-12-06 Cilag Gmbh International Surgical instrument comprising a limited travel switch
US11849943B2 (en) 2020-12-02 2023-12-26 Cilag Gmbh International Surgical instrument with cartridge release mechanisms
US11744581B2 (en) 2020-12-02 2023-09-05 Cilag Gmbh International Powered surgical instruments with multi-phase tissue treatment
US11653915B2 (en) 2020-12-02 2023-05-23 Cilag Gmbh International Surgical instruments with sled location detection and adjustment features
US11944296B2 (en) 2020-12-02 2024-04-02 Cilag Gmbh International Powered surgical instruments with external connectors
US11737751B2 (en) 2020-12-02 2023-08-29 Cilag Gmbh International Devices and methods of managing energy dissipated within sterile barriers of surgical instrument housings
US11653920B2 (en) 2020-12-02 2023-05-23 Cilag Gmbh International Powered surgical instruments with communication interfaces through sterile barrier
US11678882B2 (en) 2020-12-02 2023-06-20 Cilag Gmbh International Surgical instruments with interactive features to remedy incidental sled movements
US11627960B2 (en) 2020-12-02 2023-04-18 Cilag Gmbh International Powered surgical instruments with smart reload with separately attachable exteriorly mounted wiring connections
US11890010B2 (en) 2020-12-02 2024-02-06 Cllag GmbH International Dual-sided reinforced reload for surgical instruments
US11751869B2 (en) 2021-02-26 2023-09-12 Cilag Gmbh International Monitoring of multiple sensors over time to detect moving characteristics of tissue
US11950779B2 (en) 2021-02-26 2024-04-09 Cilag Gmbh International Method of powering and communicating with a staple cartridge
US11723657B2 (en) 2021-02-26 2023-08-15 Cilag Gmbh International Adjustable communication based on available bandwidth and power capacity
US11730473B2 (en) 2021-02-26 2023-08-22 Cilag Gmbh International Monitoring of manufacturing life-cycle
US11793514B2 (en) 2021-02-26 2023-10-24 Cilag Gmbh International Staple cartridge comprising sensor array which may be embedded in cartridge body
US11950777B2 (en) 2021-02-26 2024-04-09 Cilag Gmbh International Staple cartridge comprising an information access control system
US11925349B2 (en) 2021-02-26 2024-03-12 Cilag Gmbh International Adjustment to transfer parameters to improve available power
US11701113B2 (en) 2021-02-26 2023-07-18 Cilag Gmbh International Stapling instrument comprising a separate power antenna and a data transfer antenna
US11749877B2 (en) 2021-02-26 2023-09-05 Cilag Gmbh International Stapling instrument comprising a signal antenna
US11812964B2 (en) 2021-02-26 2023-11-14 Cilag Gmbh International Staple cartridge comprising a power management circuit
US11744583B2 (en) 2021-02-26 2023-09-05 Cilag Gmbh International Distal communication array to tune frequency of RF systems
US11696757B2 (en) 2021-02-26 2023-07-11 Cilag Gmbh International Monitoring of internal systems to detect and track cartridge motion status
US11826042B2 (en) 2021-03-22 2023-11-28 Cilag Gmbh International Surgical instrument comprising a firing drive including a selectable leverage mechanism
US11826012B2 (en) 2021-03-22 2023-11-28 Cilag Gmbh International Stapling instrument comprising a pulsed motor-driven firing rack
US11737749B2 (en) 2021-03-22 2023-08-29 Cilag Gmbh International Surgical stapling instrument comprising a retraction system
US11723658B2 (en) 2021-03-22 2023-08-15 Cilag Gmbh International Staple cartridge comprising a firing lockout
US11759202B2 (en) 2021-03-22 2023-09-19 Cilag Gmbh International Staple cartridge comprising an implantable layer
US11717291B2 (en) 2021-03-22 2023-08-08 Cilag Gmbh International Staple cartridge comprising staples configured to apply different tissue compression
US11806011B2 (en) 2021-03-22 2023-11-07 Cilag Gmbh International Stapling instrument comprising tissue compression systems
US11786243B2 (en) 2021-03-24 2023-10-17 Cilag Gmbh International Firing members having flexible portions for adapting to a load during a surgical firing stroke
US11944336B2 (en) 2021-03-24 2024-04-02 Cilag Gmbh International Joint arrangements for multi-planar alignment and support of operational drive shafts in articulatable surgical instruments
US11903582B2 (en) 2021-03-24 2024-02-20 Cilag Gmbh International Leveraging surfaces for cartridge installation
US11849945B2 (en) 2021-03-24 2023-12-26 Cilag Gmbh International Rotary-driven surgical stapling assembly comprising eccentrically driven firing member
US11744603B2 (en) 2021-03-24 2023-09-05 Cilag Gmbh International Multi-axis pivot joints for surgical instruments and methods for manufacturing same
US11857183B2 (en) 2021-03-24 2024-01-02 Cilag Gmbh International Stapling assembly components having metal substrates and plastic bodies
US11896218B2 (en) 2021-03-24 2024-02-13 Cilag Gmbh International Method of using a powered stapling device
US11832816B2 (en) 2021-03-24 2023-12-05 Cilag Gmbh International Surgical stapling assembly comprising nonplanar staples and planar staples
US11793516B2 (en) 2021-03-24 2023-10-24 Cilag Gmbh International Surgical staple cartridge comprising longitudinal support beam
US11786239B2 (en) 2021-03-24 2023-10-17 Cilag Gmbh International Surgical instrument articulation joint arrangements comprising multiple moving linkage features
US11896219B2 (en) 2021-03-24 2024-02-13 Cilag Gmbh International Mating features between drivers and underside of a cartridge deck
US11849944B2 (en) 2021-03-24 2023-12-26 Cilag Gmbh International Drivers for fastener cartridge assemblies having rotary drive screws
US11918217B2 (en) 2021-05-28 2024-03-05 Cilag Gmbh International Stapling instrument comprising a staple cartridge insertion stop
US11826047B2 (en) 2021-05-28 2023-11-28 Cilag Gmbh International Stapling instrument comprising jaw mounts
US11723662B2 (en) 2021-05-28 2023-08-15 Cilag Gmbh International Stapling instrument comprising an articulation control display
US11877745B2 (en) 2021-10-18 2024-01-23 Cilag Gmbh International Surgical stapling assembly having longitudinally-repeating staple leg clusters
US11937816B2 (en) 2021-10-28 2024-03-26 Cilag Gmbh International Electrical lead arrangements for surgical instruments

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